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THE 



JOHNS HOPKINS HOSPITAL 



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VOLUME XXIX 



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BALTIMORE 
THE JOHNS HOPKINS PRESS 

1918 




^U Boxi (giftimore (pttee 

BALTIMORE, MD., T. 8. *. 



31 
3aT6 



BULLETIN 



OF 



THE JOHNS HOPKINS HOSPITAL 



Entered as Second-Class Matter at the 



Baltimore, Maryland, Postoffice 



Vol. XXIX— No. 323] 



BALTIMORE, JANUARY, 1918 



CONTENTS 

PAGE 



[Price, 50 Cents 



Ureteral Stricture— Report of 100 Cases. (Illustrated.) 

Hv Guy L. Hu.NNER, M.D.. F.A.C.S 1 

The Chief Function of the Oblique Muscles of the Eye. Some 
Observations Which Seem to Lend Support to a Long Dis- 
carded Theory. (Illustrated.) 

By Samuel Theobald, M. D. 1'"' 



URETERAL STRICTURE- REPORT OF 100 CASES' 



Clinical Observations on the Hemoglobin After Operation. (Il- 
lustrated.) 
By George R. Du.v.v and M. N. Wynne 17 

Members of The Johns Hopkins Hospital and Dispensary Start' 

Engaged in Military Duty 25 

Notes and News 26 

Books Received 27 



By IUy L. IUxner, M. E. 

(From the (liiiicrologiral Department of The 

Ureteral stricture or narrowiiii;- of the ureteral lumen clue 
to intrinsic inflammatory, changes in the ureteral wall is a 
disease far more common and of vastly greater importance 
than the literature or our previou.s experience has led us to 
helieve. 

In a preliminary paper read liefore the Genitourinary Sec- 
tion of the l^ew York Academy of Jledicine in January, 1916/ 
the author reported 50 cases of ureteral .stricture occurring in 
his practice up to Novemher 1, liU."). In the same period of 
13 years of practice tiiere were record.-; of 49 cases of nephrec- 
tomy for tuberculosis and 'M caNe< of stone in the ureter. In 
the 18 months since Xovendicr 1, 191.'), or since becoming alive 
to the importance of the subject, and since looking for stric- 
ture, talking stricture, and having confreres refer suspected 
cases for diagnosis and treatment, the author has seen more 
than too additional ca.ses. 

Tliis paper will deal in a statistical manner with the first 
100 ca^s only, although the general conclusions will be based 
on an experience with over 150 ca.ses, and a few of the illus- 
trations will h, of recent cases not in the first 100 but showing 
points of ]>arti.-ui.-,r diagnostic interest. 



F. A. C. S., Baltimore 
Johns Hopkins University and Hospital) 

Etioloyy. — U\) to within the past few years most of the 
literature on this subject has been devoted to the so-called 
congenital stricture of the ureter.^* 

Kelly" anticipates our more modern literature of the sub- 
ject by stating that " Strictures are caused by an inflamma- 
tion in the ureteral walls produced by the commoner pyogenic 
cocci, by the gonococcus, and by the tubercle bacillus. The 
commonest form of inflammation is that due to the tubercle 
bacillus, and the rarest in my experience in women is due to 
the gonococcus." 

Garceau," ou the other hand, says, after reviewing the litera- 
ture, and in the light of his own experience, " The chief cause 
of fibrous stricture is gonorrheal infection." 

Furuiss' took issue with the prevailing opinion that most 
ureteral strictures are congenital in origin, and from a study 
of his cases concluded that infection plays the important part 
in the production of ureteral stricture. He thinks tliat the 



' Paper read before The Johns Hopkins Hospital Medical Society, 
May 7, 1917. 

''Stricture of the Ureter, Excluding Tuberculosis and Calculus; 
Heport of Fifty Cases. New Yorli Med. Jour., July 1, 1916. 



"Bottomley: Certain Congenital Strictures of the Ureter. Annals 
of Surgery, 1910, LII, 597. 

•Elsendrath: Congenital Stenosis of the Ureter. Surg., Gyn. & 
Obstet., 1911, XII. 533. 

• Stricture of the Ureter. Jour. Amer. Med. Assn., 1902, XXXIX, 
363. 

" Ureteritis in the Female. Amer. Jour. Med. Sci., 1903, CXXV. 
2S4. 

' Jour. Amer. Med. Assn., 1912, LIX. 2051. 



JOHNS HOPKINS HOSPITAL BULLETIN 



f-No. 323 



infiltration in the ureter is the result of an acute hematogenous 
infection of the kidney, which often persists as a pyelitis, 
ureteritis, or secondary cystitis. 

Furiiiss quotes Sugimura ' as having studied the lower end 
of the ureters in the bodies of 25 patients, who had had cystitis 
but had died of other causes. He found changes of an inflam- 
matory type in the submucosa and muscularis and was of the 
opinion that the infection extended through the lymphatics 
and not along the mucosa. 

Necker" exhibited before the Deutsche Gesellschaft fiir 
Urologie, at the Congress in Vienna in September, 1911, pyelo- 
grams of cases of pyelitis, all showing some dilatation of the 
renal pelvis, and in explanation said that they were cases of 
ureteral obstruction with secondary infective hydronephrosis. 

Kelly and liurnam," speaking of traumatic stricture, voice 
our common experience in stating that " Traumatic stricture 
of the vesical end of the ureter following the injuries of labor 
and of surgical operations especially the Wertheim operation 
for cancer of the cervix uteri, is quite common. As a rule, 
the trauma has so interfered with the blood supply of the 
organ that there are lateral necrosis, a continuous leakage of 
the urine, and ureterovaginal fistula. The spontaneous heal- 
ing of such a fistula, almost invariably, means stricture." 

Gun-shot and stab-wound injuries are rare. Morris" col- 
lected reports on 5 such injuries. Figure 1 shows a stricture 
resulting from gun-shot injury and giving rise to symptoms 8 
years after tlie injury. 

Severe traumatic accidents are rarely the cause of stricture, 
as one would naturally conclude after consideration of the 
anatomy of this long flexible organ, well protected along the 
spine and attached at either end to a movable organ. Any acci- 
dent severe enougli to rupture the kidney or bladder or to 
crush the bony pelvis might well result in ureteral stricture, 
but the history would be such as to suggest the etiology in a 
case of this nature. 

Syphilis should be kept in mind as a possible cause of 
ureteral stricture." 

Ureteritis cystica may cause ureteral obstruction from the 
large size of some of the cysts, but this condition, although 

probably of iiillm ;itory origin, cannot be classified as ureteral 

stricture." 

Gynecologists might question the possil)l(y relationship be- 
tween infected cervical glands and ureteral stricture. As \vc 
shall lea in later, the vast majority of these strictures occur in 
the broad ligament region and it is only natural that we should 
suspect the cervix as having a possible causal relationship. 



'Virchow's Arch. f. path. Anat., (October, 1911. 

"Zeitschr. t Urol., 1912, III, 464. 

'" Diseases of the Kidneys, Ureters, and Bladder. Apploton, 1914, 
II, 354. 

" Surgical Diseases of the Kidney and Ureter, 1901, II, 332. 

" Proksch: Arch. f. Dermat. u. Syph., 1899, XLVllI, 224. 

"Carey and Laird: A Peculiar Hypertrophy of the Prostate 
Accompanied by Ascending Infection and Cysts in the Ureter. 
Albany Medical Annals, July, 1904. 



It is probable that ureteral stricture occurs more frequently 
in women than in men, and one is inclined to attribute this to 
the infections incident to childbirth. Opposed to this theory 
is the fact that in a considerable proportion of cases the symp- 
toms of stricture begin in childhood or occur in women who 
have never married and in whom we have no i^ason to suspect 
a gonorrheal infection. Our failure to recognii<; the disease 
in both sexes has undoubtedly been due to our igijoranee of 
its frequency and consequently to a failure to look for the 
lesion. 

Although I have not seen any reason in any individual ca^e 
for attributing ureteral stricture to a cervical infection. I 
have become suspicious of the etiological relationship between 
focal infections and certain cases of cervicitis. We have a 
type of urethral inflammation in which the vulva and para- 
urethral glands are inflamed and the patient has an inflamed 
cervix furnishing a considerable amount of leucorrhea. This 
type of inflammation is particularly likely to occur in adult 
maiden women, who show no other evidence and give no his- 
tory of onanism or of gonorrheal infection. Time will demon- 
strate, I believe, that the group of inflammatory foci in the 
pelvis are secondary to a distant common focus of infection. 

The frequent association of ureteral stricture and venous 
phleboliths in the immediate neighborliood speaks for a common 
origin for the inflammatory process resulting in the two con- 
ditions, and suggests that some of these infections may have 
originated in the genital tract. 

While we must admit the possibility and probability of any 
of the foregoing factors playing a role in the etiology of certain 
ureteral strictures, I am firmly convinced that the majority 
of ureteral strictures, excluding those of tuberculous origin, 
should be classified as simple, chronic, stricture, and that they 
have their origin in an infection carried to the walls of the 
ureter from some distant focus such as diseased tonsils, sinuses, 
teeth, or gastro-intestinal tract." This cpnception of stric- 
ture postulates that in the majority of cases ureteral infiltra- 
tion is primary, and that the other urinary tract lesions so 
often associated with stricture, such as stone in the ureter, 
hydronephrosis, pyelitis, and pyonephrosis, are secondary. 

As reported in my first paper on '' Chronic Urethritis and 
Chronic Ureteritis Caused by Tonsillitis," read before the 
1910 meeting of the Southern Surgical and Gynecologiail 
Association at ^'ashville, and as borne out by a fairly wide 
experience since that time, I have the proof that certain obsti- 
nate cases of chronic urethritis, which will not heal under the 
ordinary methods of treatment carried on over a long perio''' 
of time, will promptly become absolutely well without finiher 
local treatment by getting rid of the distant focus of infection. 

In the case of ureteral stricture it will jirobaWy take some 
years of experiiMu-c bcrorc wc can claim lo Jiavc satisfactory 



"Hunner: Chronic Urethritis and Cbronic Ureteritis Caused 
by Tonsillitis. Jour. Amer. Med. Assn., LVl, 937, 1911; Treatment 
of Pyelitis. Surg., Gyn. & Obstet., XV, 444, 1912; Diagnosis and 
Treatment of Obscure Cases of Pyelitis and Hydronephrosis. Inter- 
national Clinics. 22, IV. 1912. 



January, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



proof of the above thesis. Not only must we collect a large 
number of cases similar to Case 7, reported in the above paper, 
in which symptoms of ureteral stricture began soon after an 
attack of tonsillitis, but we must have a series of cases of 
ureteral stricture in which relief fails through a long period 
of treatments and is then obtained after the distant focus of 
infection has been discovered and corrected. 

I have a few cases which have persistently showed no material 
improvement in symptoms until after removal of infected ton- 
sils, or teeth, and another list of patients who have been dis- 
missed as well after dilatation of the strictures or after getting 
rid of the pyelitis by dilatation of the stricture and lavage, 
and who have returned with their old symptoms after a fresh 
tonsillitis attack or after undergoing dental work. 

Symptoms. — Pain is the most uni^yersal symptom of uret- 
eral stricture and only in rare cases is it absent. To attempt 
to draw a pain chart of this affection diie would need a dia- 
gram of the human frame extending from the diaphragm to 
the ankles. The most deeply shaded portion of this chart 
would center in the local area of ureteral inflammation, or in 
other words in the broad ligament region deep in the pelvis. 

In my preliminary paper above mentioned as read in New 
York, 1 said: " It is comparatively rare to have our attention 
directed to localized symptoms due to the stricture. The 
patient usually complains of jjain in the kidney region or of 
bladder symptoms or of both, and the stricture is found in 
the attempt to fathom the cause of the symptoms."' 

This statement was made after a study of my first 50 cases 
seen at a period when ureteral stricture as an entity was not 
in mind. Many of those patients came late when the kidney 
lesion was advanced and overshadowed other conditions. Since 
making that report and realizing the importance of ureteral 
stricture, better histories have been obtained, and it is rare 
to find a patient with stricture who does not complain of a 
pain or of a nagging discomfort in the site of the ureteral 
inflammation. 

From this center of inflammatory discomfort in the pelvis 
the pain may radiate in any direction, upward toward the 
kidney, laterally into the hips or groin region, posteriorly, sim- 
ulating a sacroiliac joint condition or a sciatica, and down- 
ward into the thigh and leg either posteriorly or anteriorly. 

Next in frequency to the local ureteral pain is pain in the 
kidney region. This is probably at times a referred pain from 
the inflammatory area in the ureter, but it is usually due to 
overdistension of the pelvis of the kidney. 

At times, when the renal catheter is passed and the wax tip 
and again the wax-bulb impinge upon the tender stricture area, 
the i)atient locates the pain in the kidney region. The kidney 
pain is usually elicited only by injecting the pelvis to over- 
distension. Frequently we get the history that the patient 
suffered at first with a more or less constant pain low in the 
abdomen, and that she later developed intermittent attacks 
of pain in the kidney region. Early in the patient's history 
these intermittent kidney attacks may come on only at the 
menstrual period or on getting the feet wet. or mi having 
some unusual exposure, conditions that would lavor the closure 



by swelling of an already narrowed area in the ureter. Later 
the pain in the upper flank or lumbar region may occur at 
frequent intervals or become as constant as the ureteral pain. 

Occasionally the pain occurs first in the kidney region and 
develops later in the lower abdominal quadrant or region of 
the ureteral stricture. (See Figs. 2 and 3.) 

Actual pain in the bladder occurs only in the exceptional 
case, and this is probably a referred pain from the kidney or 
ureter, as it accompanies the severe acute renal attacks simu- 
lating stone in the ureter in which there are likely to be both 
bladder and rectal tenesmus. Figure 4 illustrates such a case 
in which the two attacks of renal colic were accompanied by 
bloody urine and were controlled only by repeated hypoder- 
mics of morphin. 

Discomfort in the bladder and frequency of voiding are not 
at all uncommon in the intermittent renal attacks, and these 
symptoms may be present in patients complaining only of the 
ureteral pain. One of my recent patients, not in the first 
one hundred, complained chiefly of a nagging desire to urinate. 

Miss P., aged 51 years, had had multiple fibroids removed by 
Dr. Kelly 4 years previously. Three years later she had begun to 
have bladder symptoms and in September, 1916, she had returned 
to Dr. Kelly, who had failed to locate the cause. In May, 1917, she 
consulted me and in addition to her almost intolerable nagging 
desire to urinate, causing her to void from every hour to 3 hours 
in the day and to arise many times at night, I found that she com- 
plained of a dull pain in the left hip, of a pain high in the left 
lumbar region, and of a pain extending down the posterior left 
thigh into the calf of the leg. More recently she had developed an 
intermittent pain of less severity in the right hip and in the right 
side of the back. Investigation revealed a normal urine, a stricture 
of the urethra but a perfectly normal-appearing vesical, trigonal 
and urethral mucous membrane. The left ureter had such a dense 
diffuse stricture that 1 got by only on the third attempt in a series 
of 7 efforts within 10 weeks. 1 found a series of 4 dense areas of 
obstruction in the left ureter within 6 centimeters of the bladder, 
and that the kidney pelvis held only 6 c. c. The right ureter showed 
a dense diffuse stricture extending from the bladder to 9.5 cm. 
above, which could always be dilated; the kidney pelvis held double 
the normal quantity. Manipulation of the stricture area on either 
side caused her nagging desire to void, and manipulation of the left 
ureteral stricture caused pain in the kidney region, hip, and in the 
calf of the leg. 

Urine examination.— The urine may be quite negative on 
repeated careful centrifuging and microscopic search. If there 
is an associated pyelitis, the urine shows the pathologic features 
and variations common to that condition. If the urine is not 
infected we may still find a few leukocytes or a few erythro- 
cytes or both. These may come from an ulcer area at the 
site of the stricture, or we may find them increased in number 
after one of the acute kidney attacks, when they probably 
result from the trauma to the kidney pelvis. Figure 5 illus- 
trates a unique case of symptomless hematuria apparently 
due to ureteral stricture. 

jTecpr.— Chills and fever are common in the cases with uri- 
nary infection. A patient with an infection may go for weeks 
or months without chills or appreciable fever and, indeed, may 
be in apparently perfect health, or may suffer only from malaise 
and general depression. When there occurs any condition that 



JOHNS HOPKINS HOSPITAL BULLETIN 



[Xo. 323 



causes the stricture area to close the patient will develop fever 
(often with chills) pain and general prostration, such as are 
usually seen in acute pyelitis. 

It is important to note that a patient may develop fever 
even of a high grade without infection of the urine and with 
only one ureter involved. The urine may be quite normal or 
there may be only a few erythrocytes. The kidney is enlarged, 
tender and painful. A few of the patients with sterile urine 
have shown a slight daily rise of temperature and these are 
likely to have nausea, headache, or other uremic symptoms. 
One patient with a daily rise of temperature of 99° to 
100° F. extending over a period of four weeks, and with 
a leukocytosis of 19,000, falling in the same period to 12,000, 
had a normal temperature and leukocyte count of 10,000 ten 
days after tonsillectomy. 

Miss M., aged 22, nurse at the Hebrew Hospital, was awakened 
one Friday morning with a severe cramp-like pain in the right kid- 
ney region extending downward and forward to about the pelvic 
brim region. She had several attacks with severe pain, nausea and 
vomiting but kept on duty until the following Monday, when she 
reported to the superintendent of nurses that she could not con- 
tinue with her work. 

The first attack came on at the end of a menstrual period. For 
two nights before the attack she had been up frequently to void, 
and she had too frequent voiding up to the time of entering the 
hospital as a patient. 

Drs. Adler and Hirsh were called to see the patient and because 
of the character and location of the pain and the presence of 
microscopic blood in the urine, they considered the case one of 
stone in the kidney or ureter. X-rays were negative and they 
called me into the case on October 20, the twelfth day of her illness. 

Because of a daily rise of temperature to above 99° F. and a 
leukocytosis of 19,000 with a high percentage of polymorphs, we 
considered seriously the possibility of an appendicitis, with a high 
posterior position of the appendix to account for the pain phe- 
nomena. The presence of the above signs and symptoms without 
pus in the urine argued against a kidney lesion. Blood in the urine 
is not particularly rare in appendicitis. The patient's pain was 
more pronounced and more prolonged than one usually sees in 
appendicitis. She was rather stout, and considering the possibility 
that the X-ray might have missed a stone, I catheterized the kidney 
with a wax-tipped bougie. This came back without scratch marks. 
The meeting of the catheter tip with the kidney pelvis caused an 
increase of the patient's pain which she likened to that which she 
had had before. The injection of the kidney pelvis also exag- 
gerated her former pain and the pelvis seemed to be rather smaller 
than normal, returning only 6 c. c. after being dilated to dis- 
comfort. This test of the kidney was followed by three days of 
intense pain instead of the usual few hours of discomfort caused 
by such an examination. The patient had to be chloroformed 
several times to control the pain. The temperature conditions and 
the leukocyte count remained about the same. 

In view of the pain phenomena during catheterization and the 
great increase in pain after the catheterization, I became more 
convinced of the possibility of ureteral stricture, although there 
had been no apparent obstruction to the catheter. The possibility 
of stricture had been in mind from the first, when, on taking the 
history, I found that the patient had been troubled with her tonsils 
from time to time all her life, her last definite attack having oc- 
curred about 8 months previously. Another factor in favor of 
ureteral stricture was the presence of a dense stricture of the 
urethra. The tonsils appeared normal on examination. 

One week after the first catheterization I again catheterized, this 
time using a wax-bulb. Again I could not detect obstruction, but 



the bulb must have had a beneficial effect for the patient did not 
have the severe pain reaction. Again the kidney pelvis seemed 
rather smaller than normal. 

A week later it was time for the patient to menstruate and she 
was having increased pain in the kidney region. On catheteriza- 
tion with the wax-bulb catheter, I did not detect obstruction, but 
the wax-bulb, which was made of white wax and olive oil, equal 
parts, was partially mashed on withdrawal. A test of the kidney 
pelvis at this time when the patient was about to menstruate and 
was having increased pain in the kidney region, showed a capacity 
of 11 c. c. as compared with 6 c. c. on the two former tests. A week 
later, 5 weeks after the beginning of the patient's sj-mptoms, my 
wax-bulb was definitely obstructed at a point about 3 cm. after 
entering the ureter, and on its withdrawal it was so hung in the 
stricture area that I feared it would be dragged off the catheter. 
Fortunately I had a bulb of pure wax on this occasion and it 
returned intact. After this catheterization the patient had a good 
deal of pain for an hour or two, due to the trauma incident to the 
dilatation of the stricture of the urethra and of the ureter. There 
was none of the increase of kidney pain as on former treatments. 
A few days later I again dilated the ureteral stricture with a wax- 
bulb of about 4 mm, diameter and then referred the patient to 
Dr. Lee Cohen for tonsillectomy. Dr. Cohen reported that on 
superficial examination the tonsils appeared healthy, but at opera- 
tion they were found to contain large lacunae of free pus. 

Gastro-iniestimil sjjmptoj7is are common. They are prob- 
ably of twofold origin, arising either as a central nervous 
system reflex or as a result of toxic absorption. We see the 
same phenomena in certain cases of stone in the ureter and in 
cases of blockage of the ureter from any cause. 

The symptoms vary from a slight nausea or aversion to 
food to the most extreme nausea and vomiting sometimes 
so persistent that starvation is threatened. Gaseous disten- 
tion is a frequent symptom. Occasionally there is complaint 
of rectal tenesmus and desire for stool. Pain just before or 
during stool is present in some cases, and is probably due to 
the passing of fecal matter over the tender peritoneum at the 
site of the ureteral inflammation. In Case 66 (see Fig. 6) 
the patient learned by experience that it was more agreeable 
to omit the meal preceding the dilatation and lavage; other- 
wise she lost it by vomiting. In Case 65 (see Fig. 7) the 
patient had suffered for a year with repeated attacks of diar- 
rhoea and had lost 40 pounds in weight. Dr. Barker had 
found that she had an associated achylia gastrica and she had 
been given the dilute hydrochloric acid. After dilatation of 
her ureteral strictures her diarrhwal attacks ceased and she 
gained 11 pounds in 2 weeks. 

Colitis may occur as a result of stricture. I recently referred 
a patient to Dr. Ernest Gaither because of much pain in the 
sigmoid region, through the left hip and in the upper flank, 
together with frequent stools in which she passed mucous 
casts. After a careful study of her case Dr. Gaither asked 
me if it could be possible that she was suffering from a ureteral 
stricture. That this diagnosis had not occurred to me in 
going over her .symptoms was the more remarkable becau.se 
slie was a patient (Case 2) reported in my paper above 
referred to on chronic urethritis and chronic ureteritis caused 
by tonsillitis. A urethritis of 2 years' duration had resisted 
treatment for several months until her infected tonsils were 
removed. Slic bad remained free from the urethral symptoms 



Januaet, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



for more than 6 years and had then begun to complain of 
the colitis which, after Dr. Gaither's suggestion, I found to 
be due to a dense stricture of the left ureter. Manipulation 
of the stricture area and injection of the slightly dilated kidney 
pelvis did away with all of her discomfort on the left side, 
and her colitis symptoms ceased after the second ureteral dila- 
tation. 

Menial Sytnptoins. — One of the remarkable results of this 
study has been to find that in a patient who may have one 
normally functioning kidney and only a slight degree of stasis 
on the opposite side there may supervene mental disturbances, 
headaches, nausea, fever, and a general picture usually asso- 
ciated with the uremic state. Figures 8 and 9 are from a 
patient who had a ureteral kink due to a fan-shaped band of 
adhesions which suspended her sigmoid to the posterior peri- 
toneum just above the pelvic brim region. While in the recum- 
bent position, taking a " rest cure," to many of which she had 
been subjected during the 20 years of her symptoms, she would 
take on weight and be comparatively well. As soon as she 
returned home and attempted to lead a normal busy life, the 
weight of the sigmoid displaced her ureter and again caused 
her " spells." These attacks consisted of a fever ranging from 
99° to 100° F., malaise, headache, and a slight pain in the 
left lumbar region. The patient could " taste her fever " and 
tell by this peculiar reaction just where the thermometer would 
register within one-tenth of a degree. It is impossible to say 
what share toxemia played in her mental condition and how 
much of it was due to the disappointment and worry over her 
inability to get well. During her first 6 weeks under Dr. 
Barker's care it was considered essential to keep her in a barred 
room and have the constant supervision of a nurse. 

The urine was quite normal and X-rays of the abdomen 
were negative. Dr. Barker asked me to investigate the left 
kidney because of the slight lumbar pain accompanying her 
attacks. After freeing the adhesions between the sigmoid and 
the left ureter peritoneum the patient made a prompt and 
full recovery and wrote me 6 months after the operation that 
she had gained 23 pounds. 

Another case showing marked mental symptoms due to 
obstruction in one ureter was that of a physician who suffered 
for about a year with a morbid mental state entirely foreign 
to his usual buoyant disposition. Delusions and hallucina- 
tions worried him daily and, as in the case above reported, 
suicide became an urgent impulse. He was entirely relieved 
-after Dr. George Walker had dilated a ureteral stricture. 

Morbid Anatomy. — We have had opportunity to study the 
stricture macroscopically in about 15 operation cases. The 
inflammatory area varies from a slight annular thickening in 
the ureteral wall to a condition of diffuse cartilage-like thick- 
ening which may occupy several centimeters of the ureter and 
form a mass a centimeter in diameter. Multiple annular 
strictures are not uncommon. 

The infiltration may be confined to the ureteral wall or 
there may be much periureteritis. Often at operation one 
cannot tell by palpation whether he is dealing simply with 
a stricture or with a stricture containing a stone. 



I have had opportunity to study the stricture microscopically 
in only 3 cases (Cases 6 and 26) in which resection of the 
ureter and implantation into the bladder was performed, and 
in Case 50, in which we did a nephrectomy. The microscopic 
picture is one of chronic inflammation of all coats of the 
ureteral wall; the epithelium is changed from the transitional 
stratified type to a more squamous type and in one of the 
specimens there was an ulcer with loss of the epithelium. 

Location of the Stricture. — The stricture is located in the 
broad ligament region or within 6 cm. of the bladder in by 
far the greater number of cases. The next most frequent 
location is at the bifurcation of the internal iliac vessels or 
about 8 to 10 cm. above the bladder. This is from 3 to 5 cm. 
below the pelvic brim. In both of these regions we have a 
group of lymphatic glands and at operation these are some- 
times found enlarged. 

Contrast these locations with the generally accepted view 
that ureteral stricture is congenital and occurs at the points 
of congenital narrowing, namely where the kidney pelvis enters 
the ureter, at the pelvic brim, and in the bladder wall area. 

In the preliminary report on my first 50 cases, 18 were 
reported as bilateral. Since then in 3 of the 38 cases, reported 
as monolateral, the patients have returned with stricture on 
the opposite side. Of the 35 monolateral cases, 20 were on 
the right and 15 on the left. Of these 65 ureters with stric- 
ture the lesion has been located within 6 cm. of the bladder 
in 56, at the region of the bifurcation of the internal iliacs 
in 8 cases, and next to the kidney in 1 case. 

In my second list of 50 cases, 15 were bilateral; and of the 
35 monolateral cases, 23 were on the right and 13 on the left. 

Of this second list of 65 ureters the stricture was located in 
the broad ligament region only, in 51, in the iliac gland region 
only, in 1, and in both broad ligament and iliac gland region, 
in 13. In many of the last group of ureters with strictures 
in both iliac gland and broad ligament regions the wax-bulb 
could be felt to jump through several stricture areas and it is 
probable that in these cases of multiple nodes of thickening 
there was a condition of diffuse stricture. 

Effects of the Stricture on the Upper Urinary Tract. — Of 
the utmost interest is the relationship between ureteral stric- 
ture and other lesions of the urinary tract. This study has 
done much to explain the etiology of many urinary tract lesions 
concerning which we have had erroneous ideas in the past. 

The profession has become accustomed to view slight dila- 
tations of the pelvis and ureter as secondary to an infection 
of the urine. It is even held for the early cases with only 
slight dilatation and sterile urine that the dilatation was due 
to a previous infection. 

This view, so generally held, is well expressed by Braasch : " 
"Any considerable degree of infection involving the renal pelvis 
and ureter will be followed by dilatation. This dilatation is not 
caused by mechanical obstruction, but is the result of ciianges 
in the tissues and consequent retraction in the walls of the 
pelvis and ureter. The dilatation may vary from a scarcely 



" Pyelography: W. B. Saunders Company, 1915, 145. 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 323 



recognizable irregularity of the calyces or ureter to complete 
destruction of the pelvis. Evidence of an inflammatory pro- 
cess which has once caused dilatation will rarely be entirely 
obliterated. Such inflammatory changes in the pelvic or 
ureteral outline may be the only evidence of previous infec- 
tion. The character and degree of an inflammatory process 
can often be determined better by means of the pyelouretero- 
gram than by any other method." 

A priori one would expecl the inflammation and infiltra- 
tion to result in shrinkage rather than in dilatation of the 
tract. 

While conceding that it is possible for the urine to become 
infected at the same time that the infection, which is to result 
in the future stricture, is laid in the ureter wall, I think these 
.studies prove conclusively that the usual sequence is focal 
infection settling in the ureter wall, stricture formation, 
stasis and secondary infection of the urine. 

Although we believe we have demonstrated that most cases 
of dilatation of the kidney pelvis are due to mechanical obstruc- 
tion in the form of ureteral stricture, a surprising development 
has been the fact that many cases of ureteral stricture causing 
typical .symptoms are not associated with a dilated pelvis, and 
when the pelvis is not dilated, it is often contracted. These 
patients with contracted pelves are usually the most sensitive 
to manipulation and the contracted pelvis is probably explained 
by assuming that the extremely sensitive stricture area keeps 
up a constant pain reflex, causing a tonic spasm of the mus- 
culature of the tract above. In some cases the urinary analyses, 
functional test, and pyelograms indicate that the shrunken 
pelvis is probably due to a secondary chronic interstitial 
nephritis. (See Fig. 12.) 

Pyeloureterograms of these cases show that in some the 
ureter seems contracted as well as the kidney pelvis (Figs. 10 
and 11) and that in others the pelvis is contracted while the 
ureter is sligiitly dilated (Figs. G, 11^, 12 and 13). In some 
of these cases the pyelogram shows a larger pelvis than one 
gets by measurements. Figure 11 shows an apparently normal- 
sized pelvis, but the capacity tests showed a tolerance of 
about 4 c. c. 

In several patients with normal-sized or contracted pelves 
when first seen, the general symptoms have improved under 
repeated dilatations, but the kidney pelvis has in the same 
time developed a slight hydronephrosis. The probable explana- 
tion of this phenomenon is that a tender ulcer in the stric- 
ture area has healed under treatment, thus releasing the reflex 
spasm, but that the stricture is den.se enougii to keep up 
partial obstruction in spite of the dilatations. 

The 2 groups making up my first and second list of 50 
cases, respectively, illustrate strikingly the effects on the upper 
urinary tract when ureteral stricture is neglected. 

The first group of 50 cases consisted largely of patients 
seen incidentally at a time when ureteral stricture was not 
being looked for. In general, in this group of cases it is 
seen that there is a rclationsbip between the lapse of time. 
increase in the size of the pelvis, and develoi)mcnt of secondary 
infection. As already indicated above, tlie sccoiul group of 
cases shows many exceptions to this rule. 



In the first group of 50 cases there was no report on the 
condition of the urine in 6 cases. I have notes on cultures 
from 27 of the remaining 44 eases. In 9 of these the urine 
was sterile. Of the 17 cases in which there was no mention 
of cultures, the urine from the kidney was free from leuko- 
cytes in T, and was presumably sterile, which would make 16 
out of 44, or over 33.3 per cent of the reported cases, sterile. 
In 10 of these 17 cases without mention of cultures there was 
pus in the specimen catheterized from the bladder, and in 7 
of these the kidney specimen is also reported as yielding pus; 
so that possibly all 10 cases were infected. 

In the 16 non-infected cases the average age was 38 years, 
the average duration of symptoms 2^ years, and the average 
size of the kidney pelvis in 10 of the cases was 19 c. c, 3 of 
these holding S, 11, and 12 c. c. respectively, and the others 
holding from 15 to 30 c. c. In one exceptional case with 
symptoms of 4 years' duration the pelvis had reached a capa- 
city of 360 c. c. without becoming infected. In 5 cases there 
was no note on the pelvis capacity. 

In the 18 infected cases the average age of the patients was 
35 years, the average duration of symptoms was 4 years, and 
the average capacity of the kidney pelvis in 15 cases in which 
a record was made, was 98 c. e. In 4 of these 15 cases the 
pelvis was of normal capacity, 7 to 8 c. c, showing for the 11 
dilated cases an average capacity of 130 c.c. In the cases in 
which both pelves were dilated the capacity is figured on the 
larger pelvis only. 

In the IS infected cases of the first group the colon bacillus 
was grown in 13, in 5 of these from both kidneys. In 4 
cases a staphylococcus only was grown, in 1 case a pure typhoid 
culture \vas obtained (nephrectomy for large pyonephrosis 
soon after typhoid fever). In one of the colon bacillus cases 
f^. coli was grown from one kidney and a staphylococcus from 
tlio other, making 5 cases in which a staphylococcus was grown. 

In the second group of 50 cases all were studied baeterio- 
logically. In 11 there was an infection, in 8 with the colon 
bacillus (4 bilateral), in 1 with a staphylococcus, in 1 with 
a streptococcus, and in 1 an unidentified organism. Taking 
into consideration the I bilateral infections there were 15 
kidneys involved, and only 4 of these showed dilatation, 
measuring respectively 15. 14. •-'n. and 15 c. c. Three of the 
kidneys measured 7.5 c. c. carb and the remaining S measured 

6 c. c. or less. 

In this second group of 50 cases, 15 of which showed bilateral 
stricture, notes were made on the pelvis content of 63 kidneys. 
Of these, 22 were niinnal and ranged in size from ('i to 8 c. c, 
in 8 the ca])acity was considered less than nornuil. the jielvis 
measuring 5 c. c. or h'ss. In 24 kidneys dilatation was' 
demonstrable and if wc cxchnlc the two dilated pelves in 
Case 65 (see Fig. I ) , the remaining 22 pelves showed an average 
dilatation of 16 c. c. in nuirked contrast to the nuiny large 
pelves in the first group. 

The average age of the jiatients in the second group at the 
time of consultation was 34.5 years and the average duration 
of symptoms was 5.3 years; but if we separate from this group 

7 cases of unusual duration averaging 19 years, the average 
duration of the remaining cases was 2.6 years. 



Jaxuaky, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



Influence of Ureteral Stricture on Stone, Formation. — One 
of the most interesting side-lights on ureteral disease furnished 
liy this study has been the revelation of the probable cause 
of most ureteral stones. In operating for a ureteral stone and 
finding it encased in dense infiltration tissue, we have here- 
tofore considered the inflammatory area as due to the irrita- 
tion of the stone. At present vee have abundant evidence to 
indicate that the stone results from urinary salts being de- 
posited on the inflamed surface of the stricture area. 

Every surgeon sees an occasional' case in which a minute 
stone or a nest of minute stones is found encased in a dense 
stricture area. It is quite evident that such small stones were 
not formed in the kidney and then stopped in a normal ureter, 
nor were they formed in a normal ureter. Such small stones 
could easily be passed entire through a normal ureter. 

There can be no doubt that an occasional stone formed in 
the kidney is caught in a normal ureter. On the other hand, 
I believe that some stones found in the kidney were originally 
formed on the site of a ureteral stricture and after sufficient 
dilatation of the tract above, these stones had floated up into 
the kidney where they had increased in size. Figures 14 and 
15 illustrate 2 such possible cases. Figure 16 illustrates 
another possible sequence, viz., that a stone forming in a stric- 
ture area may develop a pressure above sufficient to force it 
out of the stricture and into the bladder. In this case the stone 
was spontaneously passed from the bladder. In Case "33, the 
liatient had suffered with bladder discomfort and incontinence 
for 9 months. A stone, 15 mm. in diameter, was removed 
from the bladder. The X-ray revealed another small shadow 
in the left broad ligament region, and investigation with the 
wax tip and wax-bulb catheter demonstrated this to be a 
venous phlebolith, but the patient had 'i strictures in the 
broad ligament region and a left colon bacillus pyelitis with 
a kidney content of 21 c. c. 

In Case 71 the patient, aged 3? years, had suffered for 8 
years with left renal colic, the attacks becoming so severe 
recently that they required several hypodermics of niorphin 
for their control. The urine was smoky with blood and con- 
tained pus and a colon bacillus infection. On passing a 
catheter prepared with small wax rings at intervals of 5 cm. 
for locating the possible ureteral stone, and with one large 
wax-bulb to dilate the ureter, the catheter returned with 
scratch marks on all the rings within v'd cm. of the tip. The 
eye of the catheter contained a particle of stone and the large 
wax-bulb had embedded in its surface about a dozen particles 
of stone. The patient was completely relieved of her severe 
colic attacks and subsequently had several dilatations of the 
stricture area until her symptoms were relieved. She had the 
contracted type of pelvis, holding but 4 c-. c. Scratch marks 
were never obtained after the first treatment, which seemed 
to have entirely cleared out the incipient stone formation. 

One of the strongest arguments for the relationship between 
stone formation and stricture is the finding of bilateral sym- 
metrical stricture and a stone in one of these stricture areas, 
as has occtirred in 4 of my cases, 2 of which are illustrated in 
Figures 17 and 18. A large stone (see Fig. lOd) was removed 



from the right broad ligament area in Case 9, 5 years after 
I had been dilating strictures in the right broad ligament area 
and iliac gland region and in the left broad ligament region. 
The obstruction by the right broad ligament stricture and its 
stone had made a large dilatation of the right ureter in which 
at operation the stricture at the iliac gland region was seen 
to form a dense annular narrowing. 

0. S. Fowler, of Denver," has called attention to the pos- 
sible importance of stasis in the etiology of stone formation. 
He attributes the stasis to a kink in the ureter due to pro- 
lapse of the kidney as demonstrated by the method he has done 
so much to develop of taking pyeloureterograms in the erect 
posture. Some of his roentgenograms, however, reveal ureters 
which are dilated below the point of kinking as well as above 
and I would interpret them as being cases of unrecognized 
ureteral stricture low in the channel causing a dilatation of the 
ureter and kidney pelvis, and a prolapse of the heavy hydrone- 
phrotie kidney, causing apparent kinks in the upper ureter. 
I have several cases of stricture of the ureter showing this 
kidney prolapse and apparent kinking of the ureter, but they 
all show the ureteral dilatation down to the stricture area as 
illustrated strikingly in Figures 2 and 3. 

Influence of Ureteral .Stricture on the PyelHis of Pregnancy 
and of the Fuerperium. — Of my last seven ca.ses of pyelitis 
developing during pregnancy or soon after delivery, 3 being 
bilateral, I have been able to demonstrate stricture of the 
ureter in all but one ease. This is probably a much higher 
percentage associated with stricture than we would find in a 
larger series. In most of such cases the stricture is probably 
present before the pregnancy and the added congestion of the 
tissues after conception sets up a slight hydronephrosis which 
becomes infected during the pregnancy or immediately after. 

Some of the cases of pyelitis of pregnancy due to stricture 
clear up spontaneously after labor after the congestion and 
edema incident to pregnancy have disappeared. Others con- 
tinue as a chronic pyelitis until treated. Undoubtedly most 
of those cases of pyelitis of pregnancy which clear up spon- 
taneously or after a few irrigations with silver solution do so 
because a stricture is not present, or because the slight dilata- 
tion of the stricture incident to passing an ordinary renal 
catheter is licnclicial. 

That a case may clear up spontaneously in spite of ureteral 
stricture is illustrated l)y a patient referred by Dr. Barker 
(Figs. 12 and 13) for attacks of renal colic associated with 
chills and high temperature. Fourteen years previously Dr. 
Kelly had been compelled to perform an abortion for this 
patient because of a bilateral colon bacillus pyelitis. She had 
no special treatment for the pyelitis, returned home with an 
infected urine, and had recurring attacks of pyelitis symptoms 
on the left side during the intervening 14 years and on the 
right side for 9 years. Examination revealed very dense bilat- 
eral strictures with the kidney pelves smaller than normal; 
the ureters showed very slight dilatation. The urine contained 



"Ureteral Obstruction Causing Urinary Stasis: .\ New Etiology 
in Kidnev Stone, etc. Jour. .\mer. Med. Assn.. 1914, LXII, 367. 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 32:5 



many hyalin and granular casts and a few pus cells whicli 
were proved to be coming from the left kidney. There was 
no infection. It could verj' well be argued that this patient 
had no stricture at the time of her pregnancy and that the 
pyelitis infection resulted in later stricture formation. My 
experience with such cases leads me to take the contrary view, 
particularly as she had suffered all her life with tonsillitis, 
and because she obtained no permanent improvement from 
ureter stricture dilatations until after the badly diseased ton- 
sils were removed. 

Diagnosis. — The diagnosis of ureteral stricture depends upon 
the history, urinary examination, palpation of the abdomen 
with special reference to the kidney and ureter regions, pal- 
pation of the ureters through the vagina or rectum, cysto- 
scopy, catheterization of the ureters by specially prepared 
catheters, and roentgenography. 

The features obtainable from the history have been dis- 
cussed above under the section on symptoms. Experience has 
taught that we should suspect stricture in any patient com- 
plaining of obscure abdominal symptoms, particularly in tlie 
lower abdomen and accompanied by referred pain in the hips 
and thighs. In addition we usually lind that the patient has 
a history or shows evidence of tonsillitis, sinusitis, or bad 
teeth. 

After a relatively wide experience in the diagnosis of such 
obscure cases 1 have learned to lay a good deal of stress upon a 
history of previous abdominal or pelvic operations from which 
the patient has failed to obtain relief. In the second group of 
50 cases 34 operations had been done, 7 of which seemed to have 
been necessary and 27 unnecessary and not followed by relief. 
Four of the patients had each had 3 operations without relief 
from the original symptoms. A more recent patient, 36 years 
of age, with bilateral stricture, had spent a good portion of the 
previous 18 years in hosj)itals, having been submitted to 8 
operations, 7 of them abdominal. Figures 10, 11, 114, 15, 20, 
21, 22, 23, and 35 illustrate cases of patients who had been oper- 
ated upon ])reviously without relief from the chief symptoms. 

Of course one cannot judge accurately as to what past oper- 
ations may have been necessary, and we must keep in mind 
the frequency of ureteral stricture and the possibility that it 
may have been present with appendicitis, gall-stones, floating 
kidney, intestinal adhesions, ovarian di.sease, uterine misplace- 
ments, or any of the numerous lesions for which the former 
operations were done. Three of the above 27 operations listed 
as unnecessary were performed by myself, 2 for appendicitis, 
in which a note was made at the operation that the appendix 
appeared normal, and one for relaxed vaginal outlet and cys- 
tocele. In this last case (No. 58) pus and blood were pre- 
sent in the urine and were attributed to a severe trigonitis 
which in turn was supjjosed to be due to the eystocele. The 
patient complained chiefly of a nagging pain in the left broad 
ligament region, frequency of micturition, and partial inconti- 
nence. With the eystocele operation wo ])ucl\ered her sphincter 
muscle region and cured her incontinence, but she experienced 
no other relief from the operation and a year later we found 
that lier syni])t(iins nf Icl't-sidcd pain and |)()llui<iiiria were asso- 



ciated with bilateral stricture and colon bacillus pyelitis. We 
have dilated the strictures and cleared up her pyelitis by 
lavage and she still has a nagging trigonitis and is planning 
to have her Ijad tonsils removed. 

It is of great importance to remember that symptoms due to 
ureteral stricture often begin in early childhood (see Figs. 24. 
25, 2C, 30, and 36). 

Urinary Examin-ation and Diagnosis. — In the section on 
symptoms we stated that the urine may be quite normal. 
This has undoubtedly been a source of frequent error in the 
past. Given a patient with symptoms that suggest trouble 
in the urinary tract, we have been willing to exclude the urinary 
tract on finding a normal urine. If the patient's symptoms 
strongly suggested stone in the ureter we have had X-rays 
taken. We have the word of the X-ray experts that they 
miss anywhere from 15 to 30 per cent of iireteral stones — a 
fact that alone should call for an examination with the wax- 
tipped catheter in all cases of suspected stone. With the fact^ 
that the unassisted X-ray will miss all ureteral stricture cases 
and that the urine may be normal, we have thrust upon us a 
duty heretofore neglected, namely, to have all questionable 
cases investigated with specially prepared catheters and per- 
haps with the thorium X-ray. 

In the second group of 50 cases there were 39 without infec- 
tion of the urine. We have definite notes on the examination 
of the urine c-atheterized from the bladder in 36 of these non- 
infected cases, and it was normal in 26 cases, contained red 
blood cells in 5 cases, leukocytes in 2 cases, and both red and 
white cells in 3 cases. 

Palpation. — There is often tenderness in the renal region 
and the kidney may be somewhat enlarged and very tender 
during one of the acute attacks of pain. The usual phenomena 
of an intermittent hydronephrosis may be demonstrated if 
this condition be present. 

Palpation of the iireter over the jielvic brim may elicit 
tenderness and a desire to void. This tenderness over the 
region of the pelvic brim has led to many useless appendix 
operations. With both conditions in mind when palpating, 
one can usually differentiate between them, as the patient will 
indicate that her usual area of pain is deep in the pelvis, back 
of tiie symi)hysis, although one may elicit more tenderness 
over the pelvic brim on abdominal palpation and mistake it 
for an indication of appendicitis. 

Vaginal palpation will show the maximal tenderness to be 
in the broad ligament region in a vast majority of cases, and 
one may actually palpate the node of thickening which in 
some cases cannot be differentiated from stone in the ureter. 

One may easily mistake the ureteral tenderness for a pain- 
ful ovary. In Case 56 the patient, then aged 40 years, con- 
sulted me first 5 years ago complaining of some of the dis- 
turbances of the menopause and a nagging pain low in the 
left pelvis. She had been advised to have a left oophorectomy.' 
I found that tlie left ovary, while apparently extremely tender, 
was of less tiian normal size, feeling like a senile fibrous 
ovary. I advised against operation. She recently consulted 
me again, having suffered intermittently witli the same pain 



January, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



iind finding it recently much exaggerated after a long auto- 
mobile ride. She had also developed marked pain in the left 
kidney region and feared that she might be developing cancer. 
I suspected ureteral stricture and found on bimanual exam- 
ination, just as I had noted 5 years previously, that the left 
ovary was small and hard and apparently very sensitive. By 
carrying the ovary medianward and isolating it from the broad 
ligament region I found that it was not at all tender. Then 
by dropping the ovary and palpating the ureter by itself, I 
found the latter to be the seat of pain and tenderness. Two 
dilatations of her left ureteral stricture have resulted in a 
most satisfactory clearing up of symptoms of 6 years' dura- 
tion. There was a draining abscess at the root of one tooth 
and she was referred to her dentist to have X-rays and the 
necessary dental work attended to. 

Cystoscopy is usually quite negative, but in the occasional 
case in which the stricture is near the bladder wall there may 
be redness and edema about the ureteral orifice suggesting the 
picture seen with a low ureteral stone. One of the most sug- 
gestive points in cystoscopy is the finding of a urethral stric- 
ture when preparing the urethra for the cystoscope. Although 
stricture of the female urethra is common after a gonorrheal 
infection I have learned by experience to give its presence 
considerable weight in the diagnosis of a suspected ureteral 
stricture. We have neglected to make any note on the con- 
tlition of the urethra in many cases, but in the last 50 cases a 
note was made in 28, and in 37 of these there was a stricture 
of the uretlira. I think complete notes would have shown at 
least 60 per cent with a urethral stricture. It is curious that 
definite annular stricture of the urethra may be present in 
some eases without bladder symptoms and with a perfectly 
healthy looking urethral mucosa. 

Cathetei- Test. — The crucial test in diagnosing ureteral 
stricture is made with the wax-bulbed catheter. This, with 
other instruments used in getting past and treating stricture, 
will be described under the section on treatment. I do not 
(■(insider obstruction to an entering catheter as diagnostic 
of ureteral stricture. Eepeated obstruction at the same point 
is certainly suggestive, but for a positive diagnosis I depend 
entirely upon the obstruction or " hang " of the wax-bulb 
on withdrawal. Obstruction of the tij) at a certain point 
in the ureter and then obstruction of the entering bulb at the 
same point, and the going by of the bulb with a jump and a 
sense of scar-tissue grating, are points upon which the experi- 
enced cystoscopist may rely with a fair degree of safety ; but 
there are many conditions which may oljstruct a catheter on 
entering, and it is better to depend upon the " hang " of the 
bulb, its jump, and scar-tissue grating sensation as it comes 
through the stricture area on withdrawal. In the case illus- 
trated by Figures 8 and 9, I did not get by the obstruction 
until the third attempt at intervals of 10 days, and then 
only by changing the position of the patient from the knee- 
chest to the right lateral position while using a consideral)le 
amount of force on the catheter with the stylet in. I con- 
sidered this a stricture case because df the great difficitlty in 
LTcttinrr by, but after getting the tbdi-iuni X-rav and before 



development of the plates, I said the case was not one of 
stricture because on withdrawal of the bulb there was only the 
faintest obstruction at the pelvic brim region, just as one can 
detect as the bulb comes through the bladder wall and again 
as it comes through the sphincter urethrse. It has been a 
source of great satisfaction to my associates in this work and 
to myself to find at operation in a number of cases how accu- 
rately the wax-bulb has located the position and the number 
of strictures; and how, in other cases like the one just cited 
with ureteral obstruction but no " hang " of the bulb on 
withdrawal, the operation has explained the cause of the 
obstruction. 

Dr. Holmes, resident gynecologist at The Johns Hopkins 

Hospital, asked me to test a ureter in which he had found 

' great obstruction to the wax-tip and wax-bulb catheter on 

entering, but no appreciable obstruction on withdrawal of the 

bulb. 

Mrs. H., aged 43 years, liad been operated upon some several 
years previously, the right ovary being removed. She complained 
of a constant pain in the lower right quadrant and at times when 
this got worse she also had pain in the right back and across the 
abdomen. I found, as Dr. Holmes had done, that it was very diffi- 
cult to pass a renal catheter through the pelvic portion of the 
ureter, but that the wax-bulb returned without appreciable obstruc- 
tion. The passage of the catheter caused a pain like her former 
pelvic pain, and injection of the kidney pelvis induced her old pain 
in the right back. At operation we found that the patient had a 
much infiltrated and adherent appendix. The former ovarian oper- 
ation had been followed by a dense adhesion of the sigmoid to the 
region of the right ovarian vessels. The pelvic peritoneum was 
reddened and thickened and on opening this and exposing the right 
ureter, 1 found that it had left the peritoneum and was adherent to 
the outer pelvic wall as a result of a marked periureteritis. With 
a tape under it the ureter was lifted and explored to its entrance 
into the bladder without the discovery of any local infiltration. It 
is probable that the hooked-up sigmoid or the appendix, or both, 
caused a chronic pelvic peritonitis, and when the pelvic inflamma- 
tion grew worse, there was enough swelling of the ureteral tissues 
to cause partial stasis and her pain in the kidney region. 

Ill a recent case in which there was much discussion as to 
the diagnosis, operation revealed a ureteral stricture where 
our wax-bulb had located it, at a point beneath the uterine 
vessels, or 8 cm. from the external urethral orifice. 

Mrs. W. was referred to me In March, 1917, by Dr. Harry Adler, 
with a probable diagnosis of gall-stones and appendicitis. Roent- 
genography had shown small shadows in the gall-bladder region 
and a bismuth stasis in the ileocecal region after 24 hours. 
Because of their multiplicity and lack of special characteristics in 
her symptoms I decided to test for ureteral stricture. This was 
definitely located in the broad ligament and some of her former 
symptoms were duplicated by injection of the kidney and manipula- 
tion of the stricture. On the day of operation and after the patient 
was anesthetized, I passed a No. S renal catheter prepared with a 
large wax-bulb, and left this in place during the operation. 

Because of a wide diastasis of the rectus muscles a long mid- 
line incision was made. A definitely diseased appendix was re- 
moved, and ileocecal bands and sigmoid adhesions were freed. 
Gall-stones were palpated and before making the separate gall- 
bladder incision 1 investigated the ureter. With its contained 
catheter it was easy to palpate the ring of thickening in the broad 
ligament region. The posterior peritoneum was opened to expose 
the ureter and an assistant then removed the catheter. It slid out 



10 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 323 



easily until the bulb caught in the stricture area, when the tug 
displaced and straightened the lower half of the pelvic ureter. 
After the catheter was out my assistant easily palpated the stric- 
ture area. 

It is important to remember that one may pass the ordinary 
renal catheter of large size without detecting a stricture. The 
presence of a hydronephrosis should make one suspect stric- 
ture and test for it with the wax-bulb. In the case of a 
pyelitis in which catheterization is followed by fever or a chiU, 
one should suspect stricture and should wait at least a week 
before making the next test with the wax-bulb. Some eases 
without infection show a marked reaction after catheteriza- 
tion, having an elevation of temperature and an unusual 
amount of pain and sometimes nausea and vomiting. Any 
of these unusual reactions after the passage of the ordinary 
catheter should prompt one to test for stricture. In some 
of my pyelitis cases I have not suspected stricture until the 
patient failed to show improvement after repeated lavage. 
Figure 6 shows a case in which I had waslied with silver nitrate 
solution 6 times and then only had suspected stricture because 
of the lack of improvement in the pyelitis. 

In Case 49 (Fig. 24) I diagnosed stricture from the cor- 
respondence about the case, this indicating that the patient 
had but one kidney and that this was the seat of an infected 
hydronephrosis. She was getting lavage treatment but fre- 
quently had high fever, chills and prostration after the treat- 
ment. My correspondent also informed me that she had lost 
one kidney by operation at the age of 22, after suffering with 
intermittent hydronephrosis attacks since babyhood, and that 
she had always been subject to tonsillitis. 

Roentgenography. — The taking of pyelouretorograms is not 
necessary in making a diagnosis except in the few cases in 
which we cannot go by an obstruction in the ureter. Under 
such conditions if we can pass an X-ray catheter with a 
whistle tip to the point of obstruction, we can often get the 
contrast solution to go beyond the obstruction and intensify 
a stone, if it be present, or outline the character of the obstruc- 
tion and the condition of the tract above. 

In Case .")0 (Fig. 1.")) we failed on several occasions to get 
enough thorium past the stricture to get a shadow in the l<idney 
pelvis. Urine with pus and blood was coming from the kidney. 
In a recent case (Fig. 23) we were arrested at an obstruc- 
tion on two occasions and then had the nature of the case 
cleared up by injecting thorium beyond the stricture into the 
ectopic kidney. Later we successfully dilated the stricture and 
gave tlie patient relief from symptoms of 15 years' duration. 

Although the X-ray is not nei^essary in making a diagnosis 
in most cases of uTCteral stricture and although I refused to 
use it in my early cases 'wlien Ave were dependent on collargol 
with its dangers, I now use it in most cases for the satisfac- 
tion of its confirmatory value and because I find that thorium 
may be used with impunity if employed with judgment. ■. 

Figure 27 is from Case Ki. The patient died in uremia with- 
out passing urine for 12 days after this thorium picture was 
taken. I attribute the death not to the use of thorium but 
to tlu^ troatnu'iit of both sides at the same time, that caused 



swelling and closure of both ureters. During the lavage of 
her kidneys one at a time at intervals over the previous 4 
years she occasionally had a severe reaction — fever, chills, 
nausea, vomiting, headache, and prostration — and this should 
have been a warning not to traumatize both sides at one time. 
For work on the male subject with the unavoidable restric- 
tion in the use of instruments, the pyelogram will prove one 
of the best aids in diagnosis of ureteral stricture. 

The ureterogram is of great value in deciding whether a 
small shadow on the unaided X-ray plate is within the ureter 
or whether we are dealing with a phlebolith. This point can 
usually be easily settled in women by using the wax-tipped 
and wax-ringed catheter. In using the radiogram method 
the opaque catheter or the styletted catheter should be photo- 
graphed in the ureter, ilany stones in the ureter are in the 
broad ligament region, and this is true for many phleboliths. 
Hence, it is safer to use the bifocal method, as a phlebolith 
in the uterine vein may be superimposed on the renal catheter 
and with a flat plate we cannot make a certain interpretation. 
Of even greater value is the use of these methods to dif- 
ferentiate ureteral stricture from supposed stone in the ureter 
when tlie unaided X-ray has shown a shadow in the ureteral 
- region, ilany surgeons have had the uncomfortable experi- 
• ence of operating on at least one of these cases. The patient 
complains of symptoms suggesting stone in the ureter, the 
urinary examination confirms this view, and the X-ray shows 
a shadow in the ureteral region. 

Figure 28 illustrates a case of pyelitis occurring i months 
after the birth of a first child, and in which full investigation 
changed the diagnosis from a right pyelitis due to stones in the 
ureter to bilateral stricture with right pyelitis. Figure 29 
illustrates a case referred by Dr. Hugh Trout of Roanoke, in 
which I was fortunate enough to get by her dense stricture 
with the X-ray catheter and demonstrate the extra-ureteral 
position of the stones. Figure 30 represents an X-ray plate 
brought with a patient referred by Dr. E. L. ilortimer, as a 
case of left pyelitis dtie to stone in the ureter. Investigation 
failed to show scratch marks and demonstrated that her bilat- 
eral pyelitis following childbirth was due to stricture. Figure 
31 illustrates the case of a patient with a stone in the appendix 
and gall-stones, the symptoms being due to ureteral stricture. 
Diagnosix from 'ruberculosis. — Great care must be e.Kcrcised 
not to mi.^take tuberculous disease of the ureter for ordinary 
stricture. In 1901, 1 did a resection of the ureter and implan- 
tation into the bladder on a patient who had nmch pus in 
the urine, and an impassable thickening in the lower end of 
the right ureter. One examination had shown no tubercle 
bacilli. Tlie true diagnosis was revealed a few months later, 
when I was called to operate on the patient for intestinal 
obstruction, which was found to be due to tuberculosis. The 
tuberculous kidney was removed later and the patient made 
a good recovery. 

In October. l!ll-">. Dr. ( liarU's Austrian referred to me a 
young unmarried woman, 22 years of age, who had been having 
a great deal of ]iain in tlie left pelvis and left kidney region, 
and bladder svnnitonis for about two vears. She had had ton- 



Jaxuart, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



11 



sillitis since childhood. She had had two operations, a dilata- 
tion and curettage, and a suspension of the uterus and appen- 
dectomy. After one successful dilatation of an obstruction 
low in the left ureter and the demonstration of a pyelitis, I 
was unable on several occasions to dilate again. I was plan- 
ning to expose the ureter extraperitoneally and do a retrograde 
dilatation, when at a final cystoscopy I was impressed with 
the large amount of. edema about the ureteral orifice and made 
a second search for tubercle bacilli, which resulted in demon- 
strating them in large numbers. Nephrectomy for tubercu- 
losis resulted in a restoration to health. 

Figure 32 illustrates a case in which I had succe.ssfuUy re- 
lieved the uncomfortable symptoms by dilating the stricture 
and in which I first suspected tuberculosis because the patient's 
large amount of pus failed to diminish after repeated lavage. 
ily suspicions were increased when on getting this pyelouretero- 
gram we saw the irregularly eroded character of the pelvic 
outline. A search for tubercle bacilli was positive. 

Differential Diagnosis. — It may be well to close this section 
on diagnosis by giving a list of various diagnoses made upon 
these patients although their symptoms were chiefly due to 
ureteral stricture. Urinary tract: cystitis, pyelitis, pyelitis of 
pregnancy and the puerperiuni, pyonephrosis, floating kidney, 
hydronephrosis, stone in the ureter, chronic Bright's disease. 
Genital tract: pelvic inflammatory disease, ovarian disease. 
Gastro-intestinal tract: various functional disorders of the 
stomach and intestines, chronic peritonitis, intestinal adhe- 
sions, sigmoid adhesions, colitis, chronic pancreatitis, gall- 
stones, appendicitis. Joint and nerve conditions : lumbo-sacral 
and ilio-sacral joint pains, neuralgia of the sacral plexus, 
sciatica. Mental disorders. 

Treatment. — The chief end sought in treatment is the re- 
lief of symptoms, and in the infection cases a urine freed 
from infection, and in all cases .suitable for dilatation such 
a thorough opening of the stricture area that there will be no 
recurrence. 

There are very few ca.ses in which we cannot at least amelio- 
rate the symptoms, and fortunately we can relieve the patients, 
to a large extent, if not entirely, in the majority of cases. 
There are very few cases of pyelitis in which we fail to do 
away with the infection. I believe that time will demonstrate 
that in many cases we shall not get a permanent dilatation of 
the stricture, and complete relief of symptoms until we have 
eradicated the original focus of infection. 

The ideal treatment for stricture of the ureter is by dilata- 
tion from the vesical approach. Naturally those whose work 
is confined to women and those who use the Kelly speculum 
have a great advantage in treating this disease. Various forms 
of operative cystoscopes and ureteral instruments have been 
devised by Bransford Lewis and others, which make it quite 
possible to do mucli effective work from the vesical end in 
the male. 

My work being confined to women, I shall speak only of 
the methods which I have used in treating stricture, these 
having been largely developed or suggested by Dr. Howard A. 
Kelly. 



A glance at Figure 33 will show the simple instruments 
which I use, entirely with the tubular speculum of Kelly. As a 
rule I use the olive-tip catheter (Xos. 7, 8, and 9) carrying 
a wax-bulb 8 to 10 cm. from the wax-tipped end (b). Not 
infrequently, when the olive-tip catheter refuses to pass, a 
round-tip (a) or a whistle-tip (c) will engage in the lumen and 
go by the stricture. One may use the ordinary whistle-tip 
catheter with the wax-bulb or the whistle-tip catheter with 
a gradually increasing diameter, which Garceau devised for 
the special purpose of making functional tests (c). This 
Garceau catheter (Nos. 11 or 13) gives a fairly good dilata- 
tion without the addition of the wax-bulb. 

At times these catheters engage in the lumen of the stric- 
ture area better with the wire stylet left in for stiffening, and 
at times a slight withdrawal of the stylet will result in success 
when the catheter has seemed permanently obstructed. 

In case of failure to get by with any of these forms of 
flexible catheter, it is sometimes possible to make the first 
entrance with the metal searcher (f). By slightly curving 
the last centimeter of the metal searcher, one can gently rotate 
the angled handle, thus giving the tip a variety of axes, in one 
of which it will engage and jjass the stricture where the more 
flexible instruments will meet a pocket or shelf of mucosa 
and be permanently obstructed. Usually after getting through 
the stricture area with the olive-pointed metal searcher, one 
can withdraw the searcher and immediately get by with one of 
the flexible catheters which has previously been held ; or one 
can follow the metal searcher with the metal bulb dilator (g), 
which has a slightly curved olive-tip, followed by a metal bulb. 
3 mm. in diameter, which gives such thorough dilatation that 
the flexible catheter is quite certain to pass. At later treat- 
ments, where a still greater dilatation is desired, the metal 
bulb dilator 5 mm. in diameter (h) may be used. It is 
seldom necessary to use this large metal bulb, for one can 
easily use the flexible catheters with a wax-bulb as large as 
6 mm. in diameter. In using these very large bulbs it is well 
to see that the bulb is of a perfectly spindle shape, having no 
abrupt shoulder to catch on the stricture. 

In our earlier work in testing for stone in the ureter we 
always iised beeswax (thcjcera flava or cera alba of the phar- 
macopccia) mixed with one-third or one-half of sweet oil, but 
I found that this softens the wax to such a degree that it 
is partially crushed on coming to a narrow orifice, or later on 
meeting the stricture; somtimes on withdrawal of the catheter, 
a part or all of the wax is left on the proximal side of the 
stricture. For these reasons I have given up the mixed wax 
and oil and use only the pure beeswax. This is soft enough 
to get a good impression from a stone, and it is firm enough 
to hang to the catheter and not be crushed under any ordinary 
condition of obstruction. 

At times on failing to get any of the above instruments to 
engage in a stricture, I have succeeded in making the first 
dilatation by using the whalebone filiform searchers (e). 
Usually the first two or three searchers catch in the mucosa just 
as the other instruments have done, but after introducing three, 
four, or five filiforms, one can by careful manipulation get one 



12 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 323 



of them through the, stricture lumcu, and then on further 
manipuhition the others can be made to follow. 

After dilatation with from two to four filifornis, one can 
withdraw these and pass the renal catheter with the bulb, but it 
is generally safer to leave one or two of the filiforms as a guide 
and pass the metal searcher or the flexible catheter along- 
side the filifornis to engage the stricture lumen before the 
guides are withdrawn. 

Before beginning work with the whalebone filiforms one 
should have sterile hands or put on a sterile glove, for these 
have to be grasped close to the speculum at a portion of the 
filiform that later enters the bladder or the ureter. 

Finding bj- experience that the whistle-tip catheter often 
engaged and passed a stricture after the pointed tip had failed, 
and finding that the metal searcher with a slightly curved tip 
was a most useful instrument, apparently because a rotary 
motion enabled the curved tip to pick up different axes of 
direction in the lumen, I combined these two ideas of a beveled 
tip, and a fulcrum to throw the tip into various axes, by using 
the wax on the end of an ordinary pointed-end catheter, in a 
fashion to make a corkscrew or spiral-tip catheter (see Fig. 
34). I have been successful in passing strictures with this 
spiral tip after failing with all other instruments. One can feel 
the rotation of the catheter as the spiral tip finds its way 
through the stricture. 

Precautions in Technique. — Experience has taught a few 
precautions which should be observed in treating stricture. 
If the history points to the probability of bilateral stricture, 
never investigate both sides at the first examination, and in 
later treatments do not dilate both sides at one sitting until 
you are certain that the strictures are well dilated and that 
the kidneys will have drainage after the trauma of treatment. 
Case IG (Fig. 27) emphasizes these points. 

Do not investigate or treat a stricture too frequently. It 
seems to take about 10 days in the average case for the trau- 
matic edema of the early investigation to subside. This is 
particularly true if the last effort to dilate was a failure, for 
in such a case there is usually more trauma than in the case 
in which the catheter and dilator pass on the first effort. If 
the patient is away from home and under the expense of hos- 
pital treatment she may be restive at the .surgeon's apparent 
inactivity, and it is well to explain that greater haste is likely 
to defeat the desired end. For the patients who return to my 
office or to the dispensary for treatment I prefer to fix the 
interval at I'rom 2 to I weeks or longer, according to the 
response. 

In the pyelitis cases in wiiich we arc anxious to combine 
the pelvic lavage, we may observe the 10-day interval for the 
first two or three treatments or until we are quite certain of a 
good dilatation, then we may use lavage twice a week, employ- 
ing a small catheter (No. 5 or 6) and once in 10 days or 2 weeks 
using a No. 8 or 9 catheter witli the large wax-bulb for dila- 
tation. 

In any case do not use a huge bulb for the first dilatation. 
A 3 or 3.5 mm. bulb will usually pass without splitting the 
mouth of the ureter and without too nnich trauma to the stric- 
ture area, although this small l)>ili) may split the stricture and 



cause some bleeding. It is not uncommon in the pyelitis cases 
to have a partial closure of the stricture area after the first 
one or two dilatations with the small bulb ; this being especially 
true if these treatments are at short intervals. 

The use of large bulbs measuring 5 to 6 mm. is not without 
its danger even after the patient has had repeated treatments. 
In Case 35, the patient who had only one kidney (see Fig. 35) 
was ready to be dismissed as well when we undertook to make 
a final large dilatation. This evidently split her stricture area 
for she had intermittent suppression and passage of ureteral 
clots, and was in a precarious condition for several days until 
the bleeding stopped. 

In two of my cases the use of too large a bulb or perhaps 
the presence of a too abrupt return shoulder on the wax-bulb 
resulted in great difficulty in extricating the catheter, and on 
its retui-n the shoulder carried a complete collar of mucojas 
membrane torn from the stricture area. This of course repre- 
sents an undesirable degree of trauma in the stricture area. 

One must use care in the amount of force exerted in pushing 
the catheter in. If the stylet is still entirely in the catheter 
the end of the catheter may go through the ureter. This 
evidently happened in Case 36, and a silver nitrate injection 
of 1 : 1000 strength was left in the extraperitoneal tissues of 
the pehic brim region. This caused much pain of a peritonitie 
character which persisted for nearly a week but with no 
apparent permanent damage. In Case 29 the catheter went 
through the bladder portion of the ureter, penetrated the 
bladder mucosa, and curved back into the bladiier. 

If the stylet has been partially withdrawn there is probably 
no danger of the end of the catheter penetrating the ureter, 
but forcible pushing may result in penetration of the catheter 
wall with the end of the stylet and probable puncture of 
the ureteral wall, as occurred in a recent case without observ- 
able results. 

BesuUs of Treatment by Vesical Approach. — What can wc 
hope for in the simpler non-operative forms of treatment? 
In the cases without infection and without nuuh renal dis- 
turbance we can look for cure, if distant foci of infection 
have been removed. This was the result in 8 of my first 50 
eases. The case numbers, the duration of symptoms, and the 
pelvic contents before and after treatment are shown in the 
following table: 



15 A few weeks. 
17 !■") years. 



Pelvis after treatment 



2 months. 



-- e, ('. 
l.T C. C. 



3 years later, 15 c. c. 
2 years later, !• c. o. 
5 months later, 7.5 c. c. 



5 years before pass-l 28 c. c. !5 months later, 10 c. <•. 

ing ureteral stone.' 

2 years. [ 30 c. c. ]Xot seen after 3 treatments and 

j ; I comjilete relief of sym|itoms. 

28 9 years. ] 15 c. c. 3 yeare later: No further at- 

I tacks. Pregnant for 3 J time 

! j since treatment. 
22 c. c. 4 months later, 10 c. c. 



35 18 months 
40 |3 months. 



40 c. c. jNot seen after two treatments. 



January, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



13 



Since presenting the above table in my preliminary report 
of the first 50 eases, one patient (Case 15) has returned witli 
renewed symptoms on the left side and similar symptoms on 
the opposite side. Dense strictures were present on both sides. 
Another patient (Case 35) soon returned and her kidney 
iielvis reai.lied a capacity of 33 c. c. After the extraction of 
abscessed teeth the stricture responded to treatment and when 
last s^en several months ago, she was free from kidney sym- 
tdiiis and the pelvis held 10 c. c. 

In certain other cases, even witli infection, if tlie kidney 
pelvis is not too dilated, we get brilliant results in permanently 
clearing up the symptoms and the infection through dilata- 
tion and lavage. This occurred in G of my cases, 2 with 
bilateral stricture and pyelitis. 



Case 


Duration of 


Pelvis before 




No. 


symptoms 


treatment 




34 


11 years. 


B i 1 ate ral 
and no dil- 
atation. 


Free of pus and bacteria. 


41 


1 year or less. 


30 e.e. Staph- 


Free of pus and cocci. Pelvis 






vloeoceus. 


contents c.c. (5 months later. 


43 


4 months. 


B i lateral . 
Colon. No 
dilatation. 


Free from pus and bacteria. 


47 


Pyelitis, one week. 


11 e.e. Colon. 


Free from pus and bacteria. 


49 


10 inontlis. 


40 e.e. Colon. 


Free from pus and bacteria. 
Pelvis content 30 c. c. two 
months later. 


45 


Pyelitis 3d month 


IS e.e. Rod 


One dilatationwith 5 mm. metal 




of pregnancy. 4 


bacillus. 


bulb. Xo further symptoms. 




days' duration of 




Examined one vear later, and 




symptoms. 




urine normal. 



After presenting the above table in my preliminary report, 
two patients (Cases 31: and 13) both returned with bilateral 
colon pyelitis. The first (Case 31) was dismissed as well in 
January, 1915. She again began to have some frequency and 
discomfort in August, 1915. In January, 191G, 11 teeth were 
extracted by Dr. Brun, all having bad areas about the roots. 
She returned in January, 1917, complaining of bladder symp- 
toms and general malaise as on her first visit. After getting 
the bladder approximately normal and still finding a good deal 
of pus in the urine, I investigated both kidneys in April 
and found bilateral strictures and pyelitis. The right kidney 
•vas sterile after 2 treatments with 1 : 500 silver nitrate .solu- 
tior. The left kidney still showed some infection June 1, but 
she was. practically free from symptoms and her general health 
liad improved markedly. 

The other -woman (Case 43) was dismissed as well in July. 
1915. In January, 1916, she returned during an attack of 
grippe, fearing that her trouble had returned. Investigation 
of the kidneys showed negative cultures and the ureters ap- 
parently well dilated. In February, 1917, the patient was 
" run down " and had a " slight cystitis attack." She reported 
in April, 1917, when bilateral pyelitis was found. The left 
side cleared after a few treatments, but the right side still 
shows infection (Juno 1, 1917). 

In other cases with infection and large pelves we mav bo- 
tmable by lavage to rid the patients of infection, probably 



because of the permanently sacculated pelves, but we may 
restore them to apparent health by doing away with the obstruc- 
tion in the ureter, thereby relieving their pain and their toxic 
symptoms (see Fig. 27). 

In the following 2 cases with infection the symptoms were 
relieved by treatment, but I have been unable to follow the 
patients with a cystoscopy to learn of the final kidnev con- 
dition. 

In Case 14 there were attacks of pain in the kidney for two 
years, enlarged inflamed tonsils, and arthritis, a stricture 
about 3 cm. from the bladder, and a kidney pelvis of 12 c. c. 
capacity with a stapliylococcus infection. After a few dis- 
pensary treatments she was lost track of. 

In Case 23 there was a stone in the bladder to which all 
the symptoms were referable. The X-ray picture revealed 
another small shadow in the left ureteral region. On investi- 
gation this sliadow was found to be outside the ureter, but the 
ureter had a stricture in the bladder portion and another about 
4 cm. from the bladder. The kidney pelvis held 21 c. c. and 
was infected with the colon bacillus. After a few treatments 
the strictures were well dilated and the pelvis reduced to 
14 c. c. The patient went to her home in North Carolina 
before the infection had disappeared, but a recent letter, 4 
years after her treatment, states that she is perfectly well. 

In another group of 3 cases of bilateral, infected pyelitis, 
tlie method has not had a fair trial, because of a failure of 
the patients to persist with treatments after securing enougli 
dilatation to free them from the severe attacks of pyelitis. 

Of my second group of 50 cases many are still being treated. 
Fifteen have been dismissed as well. Thirty-one are classed 
improved, some of these being practically well, others but 
little improved. Three had but 1 preliminary investigation 
and have not been seen since. One had several painful treat- 
ments without apparent improvement and, on lieing urged 
to have some bad tonsils removed, she ceased treatments. 

Treatment by Operation. — When all the methods of vesical 
approach fail, we have to consider operative measures. No 
form of operation should be undertaken until as complete 
investigation as possible has been made of both sides. Stric- 
ture of the ureter being bilateral in 30 per cent of the cases, 
we cannot afford to take anything for granted in dealing with 
a case in which symptoms may be confined to one side. 

If investigation shows stricture of only 1 ureter, associated 
with a kidney of Little or no functional value, conservatism 
usually calls for extirpation of the injured or dead kidney. 
This was done in 6 of my first 50 cases with entirely satis- 
factory results. 

If the stricture is high at tlic junction of the kidney pelvis 
with the ureter, we may follow Fenger in doing some form of 
pyelo-ureteroplasty. Actual stricture at this point is extremely 
rare, and the valve-like obstruction formed by floating kidney 
can usually be overcome by mere high fixation of the kidney, 
as I have found in a number of cases. 

If careful examination at the time of operation leads one to 
suspect an organic narrowing at the pyelo-ureteral junction, 
a pyelotomy and careful dilatation may be done in addition 
to the kidnev fixation, or if tlie pelvis is very large, a partial 



14 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 323 



pyelectoni)- may be tlouc, care being taken to dilate if tbe 
orifice into the ureter is at all narrowed. 

In Case 44 with symiitoms of 4 years' duration there was 
a stricture in the left broad ligament region and a kidney 
content of ;5C0 c. c. of clear urine, the functional test being 
good and equal on both sides. I resected her kidney pelvis 
and later examination showed tbe restored ]ielvis to hold 
T..1 c. c. 

If the stricture is lower and about the lumbar or pelvic 
brim region, it has been recommended to cut through above 
the stricture and implant into the colon or in the loin region. 

If the stricture is low and near tlie bladder, as a vast 
majority of these strictures are, it has been the custom to 
implant the severed healthy end into the colon or bladder. 
I have never made a colon implantation in these cases, l)ut 
the results of Coffey's work on dogs " and of Charles ilayo's 
work on the human, with Coffey's method, would indicate that 
there is a field for this method. Some of these patients have a 
degree of dilatation of the ureter, which would make the opera- 
tion easier than on the normal ureter, and some of them have 
such a wide dilatation of the ureter that the operation would 
be more difficult and the lowered resistance of the kidney 
would invite infection. 

I have done a bladder implantation in "i of tiie lirst Kii) 
stricture cases with indifferent or questionable results in both. 
I say " questionable results " because in neither case could I 
later enter the ureter with a catheter from below. Both pa- 
tients have been in good health since the implantation, but 
I susi)cct in hoth of these cases that there may have formed 
stricture at the site of the implantation with gradual destruc- 
tion of the kidney. 

Belrofffad Dilalalion. — I wish to emphasize a niclboil for 
handling these cases by operation wiiicb i have not seen men- 
tioned in the literature but which I am sure must have been 
employed by some surgeons and which has probal)ly been 
described before, viz., the treatment by retrograde dilatation. 
Certainly every surgeon must follow his ureteral stone extrac- 
tions by dilatation of the usual area of infiltration about the 
stone. 

The ureter is exposed by the cxtrajieritoneal route; incision 
is made into its dilated portion above the site of stricture, 
and increasing sizes of the French gum elastic bougies (Fig. 
33d) or metal sounds are passed until the stricture is dilated 
to a diameter of from -5 to 7 mm. The ureteral incision is 
then closed with catgut. A wick drain is usually left in the 
extraperitoneal incisipn for 48 hours to take care of possible 
contamination by the escaped urine at the time of operation, 
or of post-operative leakage and the excessive serum secretion 
following the extraperitoneal operation. 

If the dilatation has not been entirely satisfactory or if 
there has been much trauma to the ureter, I leave it open or 
close it incompletely with catgut to favor urine drainage in 
case of temporary swelling sufficient to close the traumatized 
stricture area. In such cases 2 or 3 small wicks are dropped 



'Jour. Amer. Mccl. Assn., 1911, Feb. 11, 397. 



to a point near the ureteral incision and left for some davs 
or until there is certainl}- no urine leakage. 

A McBurney incision is suitable for most of these cases, 
hut a semilunar line incision is more useful, for it can he 
enlarged up or down to suit the exigencies of the case, and 
through a moderately^ long semilunar line incision one can 
easily palpate from kidney pelvis to bladder. 

With care one can preserve the intercostal vessels and i^rves 
crossing this incision to the rectus muscle simply by deflectiH<r 
them and working between them. 

I have treated 9 of the first 100 eases by this retrograde 
dilatation, 6 cases in which it was impossible to dilate from 
below, 2 cases in which stricture of the ureter was found when 
stone was being looked for, and 1 case in which ureter stric- 
ture had been successfully treated from the vesical approach 
one year previously, but the stricture again swelled shut suffi- 
ciently to cause kidney symptoms in the course of an attack 
of acute gonorrheal salpingitis. 

The results in these 9 cases treated by retrograde dilata- 
tion have been perfect in 7, so far as measured by relief of 
symptoms and ability to easily catheterize later from below. 
In one case, my first one in which I was looking for stone and 
failed to find it but found the ureter dilated to a diameter 
of 1 cm. from the bladder to the dilated kidney pelvis, I found 
a dense stricture in the bladder area and dilated it with the 
uterine sound only, which probably made a diameter of only 
3 mm. I heard one or two years later that this patient devel- 
oped symptoms again and had a stone removed from the kidney. 
I have questioned the accuracy of this report, especially as the 
patient had the kidney removed at a third operation. It is 
possible that I overlooked a floating stone temporarily lodged 
in a kidney calyx, Init I think it more likely that the symptoms 
returned and persisted because the stricture was not sufficiently 
opened. ^ly X-ray picture had shown a questionable shadow 
in the kidney region. 

My second ca.-se with a questionable result after retrograde 
dilatation was one in which the stricture of the left ureter 
was a diffuse one, reaching from the bladder to 5 or (5 cm. 
above. The woman had a stricture of the right ureter also, 
but no symptoms pointing to this side. A few weeks after 
retrograde dilatation she again showed signs of kidney obstruc- 
tion and I failed to catheterize from below. I attempted to 
make a uretero-ve.sical implantation above the site of the stuc- 
ture, but failed to find the ureter in the midst of t.'ie scar 
tissue following the previous operation. 

The patient got along fairly well and when she was 3 months 
pregnant, some 3 or 4 years later, her physician at my sug- 
gestion tried to catheterize her ureters, but was unable to 
enter either kidney. One would suppose that with the increased 
circulation and pliability of the tissues characteristic of the 
pregnant state, this would be an ideal opportunity for dilating 
strictures of particular density. 

The cases least suited for retrograde dilatation arc those in 
which previous testing of the capacity of the kidney pelvis 
and ureter and pyelography have shown an absence of marked 



January, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



15 



enlargement of the lumen above the site of stricture. In these 
cases the ureter is found to be too small above the stricture 
to admit large dilators, and if it is at all possible to get by 
from the vesical approach, one should be satisfied to do as 
well as possible by this route although it may require a long, 
tedious coi;rse of treatment. 

I canrot speak with authority concerning ureteral stricture 
work :o. the male. Because of the restriction in the use of 
insti'uments, it is probable that retrograde dilatation will be 
resorted to much more frequently in the male than in the 
female. Dr. Bransford Lewis has devised a clever flexible 



metal dilator which will undoubtedly be of use in some cases. 
In many cases this instrument will be found to be too blunt 
to get by the stricture area. Those who use male instruments 
that take a No. 8 or No. 9 renal catheter will be able to relieve 
many cases merely by passing the catheter, particularly if the 
dilatation can be repeated every few weeks or months. In 
the past, many patients suffering from hydronephrosis and 
from pyelitis due to stricture have been improved or cured of 
their symptoms without discovery of the stricture because the 
passage of a renal catheter gives' sufficient dilatation in some 
cases to result in good drainage. 



THE CHIEF FUNCTION OF THE OBLIQUE MUSCLES OF THE EYE 

SOME OBSERVATIONS WHICH SEEM TO LEND SUPPORT 
TO A LONG DISCARDED THEORY 

Bv Samuel Theobald, il. 1).. 



Clinii-al I'roffisior of OpJiiluilmology, Johns Hopkins Unirers 
Hospital and Baltimore Eye, Ea 

In endeavoring to find an answer to the question. What is the 
chief function of the oblique muscles of the eye?, it is im- 
portant that we should take into account the fact that these 
muscles are not peciJiar to man, Ijut that, on the contrary, they 
are found, almost without exception, in all vertebrates — the 
only exception being the myxinoids or lampreys. This fact, 
which shows that they were evolved many thousands of years 
l)cfore even the anthropoids made their appearance, seems to in- 
dicate that they have a much more important function to serve 
than that which is commonly attributed to them in man — that 
their chief office is to counteract the faulty action of the 
superior and inferior rectus muscles, owing to the fact that 
the direction of the pull of these muscles does not correspond 
with the sagittal axis of the eyeball. Surely these conditions 
do not exist generally in vertebrates, and, therefore, could 
have had no bearing on the evolution of the oblique muscles. 

In the early part of the last century, the commonly accepted 
view, which, according to Prof. Joseph Pancoast, dates back 
to the time of Boerhaave, was that the oblique muscles were 
the antagonists of the recti and, especially, that they prevented 
"'ttie latter, when acting, from retracting the eyeball into the 
orbk. This view, however, was not without its opponent, and 
the first instance I have found of its rejection occurs in an 
article by Green,' in which the author says : 

To the favorn.? doctrine of most anatomical writers, we cannot 
subscribe, viz., that the obliqui are the antagonists of the recti. 
This error is based on another, viz., that there is a necessity for 
antagonism, i e.. that th., recti retract the ball from its ordinarv 
position in the socket. 

It is to he regretted that, at least in the published abstract 
of his paper, the writer adduces no facts or observations to 
sustain, these very positive assertions. 



tij, Medical Department; OpIitJialmic Surgeon, Johns Hopkins 
'• and Throat Hospital, Baltimore 

Coming down, now, to a more recent time, we find that so 
careful an observer as Fuchs held that some provision is neces- 
sary to prevent the eyeball, when performing its movements, 
from leaving its place in the orbit, and, according to his view, 
it is the bulbo-orbital fascia which provides against this mis- 
adventure." He says : 

By means of this system of fascia pervading the orbit, the 
contents of the latter are fixed in place. It is owing to them 
that the eye does not leave its place when performing its move- 
ments, but turns about a fixed center.^ 

This view of the action of the bulbo-orbital fascia, I may 
add, is held, also, by Duane,* another high authority on the 
ocular muscles and movements, who recently said : 

The position of the eye in the orbit seems to me to be governed 
mainly by the fascial bands (including the check ligaments) that 
connect the eye and muscles with the orbital walls. 

It requires no little temerity on my part to call in question 
the competence of the bulbo-orbital fascia to do what these 
authorities agree in holding it does do — to prevent the eye 
from leaving its place in the orbit, when the recti muscles 
contract, and to cause it to turn about a fixed point. 



'Green, C: On the Functions of the Oblique Muscles of the 
y°. Abstr., Boston Med. and Surg. Jour., 1845, xxxii, 191. 



' Motais, discussing the fixity of the eyeball in the orbit, in his 
treatise on the " Anatomie de I'appareil moteur de I'oeil de I'homme 
et des vertebres " (1SS7, pp. 123-124), answers the question, How 
can an organ with such yielding walls, immersed in a soft mass, 
and subject to such rapid movements, maintain a fixed position?, by 
saying that it is due to the combined action of several anatomic 
elements, which he mentions in this order: the antagonism of the 
rectus and oblique muscles, the bulbo-orbital fascia, with its liga- 
mentous wings, and the cushion of adipose tissue which occupies 
the deeper portion of the orbit. 

'Fuchs: Text-Book of Ophthalmology, fourth American edition, 
p. 689. 

* Personal communication to the author. 



IG 



JOHNS HOPKINS HOSPITAL BULLETIN 



[Xo. 323 



To effect this end, it would seem there must be tense, in- 
elastic bands of fascia connecting the sclera or Tenon's capsule 
with points on the orbital walls anterior to their attachments 
to the eyeball. That these l^autls must be, as I have described 
them, tense and inelastic, appears obvious; otherwise, having 
no power of contraction, they could not effectually oppose the 
very real backward pull of the several recti muscles. 

Do such fascial bands exist? And, if they did, would they 
not, acting as check ligaments, necessarily interfere with the 
movements of the eye? 

These questions, it seems t(j me, admit of hut one answer: 
Xo such bauds do exist, and. if they did, the rotational move- 
ments of the eyeball would certainly l)e seriously curtailed. 

Accepting the view of Fuchs, which I understand that 
Duane endorses, that some provision is necessary to prevent the 
eye being pulled back into the orbit by 'contraction of the 
rectus muscles, and thus enabled to rotate about a fixed point, 
it would appear that we must fall back on the discarded theory 
of the supporting or antagonistic action of the oblique muscles 
for a solution of the problem. 

If this view is correct, it would seem to follow that the 
oblique muscles must take part in all movements of the eye. 




Subjective lifjht sensations seen in left half of visual field by right eye : a, produced 
by lateral rotation of the eye ; b, b> (lowinvar<l rotation ; c, by upward rotation. The 
upper light sensation, in each instance, is caused by contraction of the inferior ob- 
ii(]ue, and the lower b^' contraction of the superior oblique. 

Observations which 1 have recently made of certain siili- 
jective light sensations, manifestly caused by contraction of 
these muscles, appear to show that such, indeed, is the case. 
with the possible exception of the conjoint action of the interiii 
in eft'cctiug convergence. On awakening in the early mornini;, 
while the room is still dark, I have observed, projected some- 
what into the upper visual field of each eye and in juxtaposi- 
tion, always -one above the other, two subjective light sen- 
sations, one decidedly sharper than the other, on rotating the 
eyes widely in any direction. On converging the eyes strongi}-. 
which I found not so easy to do in the dark, 1 have thought 1 
obtained similar light sensations, but they were less well 
defined and more evanescent than those pi-tiduced by rotating 
the eyes vertically or laterally. 

When the eyes are turned uiiward. in \\hi<'ii iii(i\cinent the 
inferior oblique should act more energetically than the superior, 
the brighter and better defined light sensation, as we .«hould 
expect, is. as shown in the illustration, above, the less dclined 
one, produced by the feebler action of the superior oblique, 
below. When the eyes are turnetl downward, the superior 
oblique being then called into more energetic action, the 
brighter sen.sation is below, the feebler one above. When the 
eyes are rotated laterally, the upper and lower light sensations 
do not differ appreciably in intensity ov in form, indieating. 



it would seem, that in these movements the obliques act with 
approximately equal energy; and the same is true of those 
which, I believe, I observed on converging the eyes. The 
phospheues seen.in the left half of the visual field are. of course, 
projected from the right eye, and vice versa. 

I may add that the light sensations described Hpidlv de- 
cline in brilliance, and, with the exception of those caused bv 
rotating the eyes upward, are best observed with the lids dosed, 
and, further, that repeated attempts to produce them, by 
energetically rotating the eyes, presently give rise to an ili- 
defined aching sen.sation, most noticeable, perhaps, in the 
region of the trochlea of the superior oblique. 

If further observation should show that these subjective sen- 
sations do not occur in convergence of the eyes for a near point, 
a possible explanation might be that in regarding near object? 
a certain amount of displacement of the eyes backward and 
inward, in addition to their inward rotation, may not be harm- 
ful, may, indeed, even be helpful, so that conjoint action on 
the part of the oliliques under such circumstances would not be 
called for. 

As to the competence of the oblique muscles to counteract 
the backward pull of the recti, and to maintain the eyeball 
in its ])roper position in the orbit, it would seem that they 
are fully equal to the task. With their fixed attachments close 
to the orbital border — that of the inferior oblique actually and 
that of the superior oblique potentially, because of its trochlea 
— and passing from these points to grasp the eyeball near its 
posterior pole, one from abo\e. the other from below, and, 
moreover, unlike the bulbo-orbital fascia, having the power to 
contract, so as to oppose with exactness the backward pull of 
the recti, the oblique muscles appear to be entirely capable of 
causing the eye to rotate, with precision, about a fixed center, a 
])rovision so essential to accurate vision, and, especially, to 
jierfect binocular vision. 

If it be objected that to do this the direction of the pull of 
these muscles would have to be straight forward, it may be 
pointed out that the pull of the recti, especially the superior 
and inferior recti, is not straight backward, and that the direc- 
tion in which the energy of the obliques is exerted seems really 
to be that best adapted to accomplish the end in view. 

That the oblique muscles serve other important ends, e.sj'cc- 
ially in preventing the superior and inferior recti from cilting 
the vertical axis of the eye. and in assisting those iuuscles to 
rotate the eyeball upward and downward, is. of course, not to 
be denied; but that their chief function is t.'iat which 1 have 
set forth seems, to me at least, to admit of hut little doubt. 



NEW PUBIICATIONS. 

Tlie following monograph is for sale by The Johns Hopkins 
Press, Baltimore, Mel.: 

Relation of Tonsillar and Nasopharyngeal Infections to General 
and Systemic Disorders. By S. .1. Chowe. S. Shelton VVatki>s 
and Ai.MA S. Rothiioitz. (>:; pages. Price, $1.25. 



January, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



17 



CLINICAL OBSERVATIONS ON THE HEMOGLOBIN AFTER OPERATION 



By Geoege K. Dunn, 
Assistant Resident Surgeon, The J olins IlopJcins Hospital, 

AXD 

H. M. X. Wyxne, 



A ssL'stant Resident Gynecologist 

There are but few observations in the literature on the 
hemoglobin of surgical patients after operation. Griiuwald in 
1889 published a series of 10 cases, from which he concluded 
that there is little or no oligochromemia immediately post- 
operative, even after abundant hemorrhage. His work, how- 
ever, does not show when or for how long the hemoglobin de- 
creases. The lowest point of the hemoglobin curve is of interest 
to surgeons as a clinical estimate of the amount of blood lost 
at operation. We have been unable to find any data on this 
point in the literature. According to Laker (quoted by 
Griinwald) immediately after operation there is no change, 
or very slight change, in the hemoglobin, but after several 
days in cases in which there has been severe hemorrhage 
there is also a great reduction of hemoglobin. After hemor- 
rhage the total blood volume is decreased, the quality of the 
blood being first changed when it becomes thinned owing to 
absorption of fluids from the intestinal tract (Hoppe-Seyler 
and Penzoldt, quoted by Griinwald ) . 

Young says that the hemoglobin immediately after hemor- 
rhage shows no especial change, but that after 6 to 12 hours 
the percentage is lowered, the fluid content of the blood seem- 
ingly adjusting itself temporarily within the first 34 hours. 

Booth by and Berry have shown that the percentage of 
hemoglobin and the red blood cells are increased under condi- 
tions of work, causing an appreciable amount of perspiration. 
and that there is no increase without sweating. 

In all probability the most important factors determining 
the hemoglobin curve, except the loss of blood at operation, 
are the intake of fluids, at or after operation, by infusions or 
through the mouth or rectum, and the output in sweat, vomitus. 
urine and feces. 

In the series of cases here reported, we have endeavored to 
show tlie efPect iipon the hemoglobin of operations during 
which there has been slight, moderate or severe hemorrhage. 

TECHNIQUE 

The 8ahli Ilemiglobinometer was used for hemoglobin 
determinations, as it is an instrument particularly adapted to 
general clinical use. 

A uniform technique was observed throughout, and in almost 
all cases one instrument was iised for all the readings on a 
given case. When two instruments were used on the same case, 
they were carefully cheeked against each other and corrections 
made, when nece.ssary. The series of readings on a given 
case were made by one observer, or, when two took part in it. 
their findings were carefully controlled and corrections were 
made v.hen necessary. 



The John« Hopkins Hospital 

In most cases the exact time of an observation has been 
noted so that the number of hours between any two readings 
can be determined easily from the tables. 

The blood was obtained from the finger or ear, the same 
source being always employed for any given patient. 

In the accompanying tables the date, time and character of 
the operation are recorded. The loss of blood at operation is 
only approximately estimated. We lack quantitative data on 
the intake and output of fluids during the entire time that the 
patients have been under observation, liut notes have been made 
of all infusions, liquids given by the rectum and of vomiting 
after operation. Unless otherwise noted, the patients ran the 
usual course, being encouraged to take water by the moiith as 
soon as possible. 

All of the gynecological patients were operated upon under 
anesthesia — nitrous oxid and oxygen, followed by etlicr ad- 
ministered by the open drop method. 

CONCLUSIONS 

The hemoglobin readings shortly after operation show very 
little change when compared with readings made before opera- 
tion, even in cases of severe hemorrhage. The immediate post- 
operative reading often shows some increase over the pre- 
operative reading. 

The lowest point of the hemoglobin curve is found usually 
from 30 to 60 hours after operation (a ditference of less than 
5 per cent is not considered). 

The greatest drop in hemoglobin is usually during the first 
34 to 36 hours, and is most rapid when salt solution infusions 
have been given. 

In the series showing only a slight loss of blood at opera- 
tion, the hemoglobin readings are usually higher during the 
first 12 hours than those made before operation, and there 
is very little post-operative decrease at any time. 

We wish to thank Dr. Howard A. Kelly for permission to 
publish these observations. 

LITERATURE 

Boothby and Berry: The Effect of Work on the Percentage of 
Hemoglobin and Number of Red Corpuscles in the Blood. Amer. 
Jour. Physiol.. XXXVII, p. 378. 

Griinwald; Hamoglobinmessungen an chirurgischen Patienten 
vermittelst des v. Fleischl'schen Hamatometers. Inaug.-Dissert., 
Wurzburg, 18S9. 

Hoppe-Seyler: Allgemeine Biologle, VI, Theil 3, p. 473, Berlin. 

Tolmatscheff: Med. Chem. Untersucliungen, Herausgeg. v. 
Hoppe-Seyler, Tiibingen, Heft. 3, S. 400. 

Young, E. B. : Emer.a;encies of Extrauterine Pregnancy. Boston 
Med. and Surg. Jour., 1915, CLXXII. 131. 



18 



JOHNS HOPKINS HOSPITAL BULLETIN 



Xo. 







TABLE I.- 


— H/EMOGLOBIN 


IN CASES WITH VERY SLIGHT BLOOD LOSS AT OPERATION 




Gyn. 
No. 


Female 


Kace 


Age 


Character of 
Operation 


Operation 
Date 


Blood Loss 

at 
Operation 


Hb. and blood counts 
before Operation 


After Operation. 
Day of Operation 


2d Day 


Day 


4th Day 


21836 


•■ 


White. 


24 


Dilatation and curettage. 


2/5/16. 
9.05 a. m. 


Very 

Slight. 


2/4/16. 

Hb. 105%. 

W. B. C. 10,000. 


7.15 p. m. 
Hb. 107%. 


7.15 p. m. 

Hb. 102%;. 


7.15 p. m. 
Hb. 103';i. 


7.30 p. m. 
Hb. 105%. 


21845 






60 


Amputation of cervix Vap. 
fl.xation of uterus Ant. and 
po.st. colporrhaphy. 


1/24/16. 
10.00 a. m. 


Slight. 


1/22/16. 
Hb. 87%. 
W. B. C. 7,400. 


9.45 p. m. 
Hb. 85%;. 


9.00 p. m. 
Hb. 86%. 


9.15 p. m. 
Hb. 95%. 


9.16 p. m. 
Hb. 90%. 


S1661 




Black. 


28 


Ether exam. 


2/17/16. 


None. 


2/16/16. 

Hb. 78%;. 

W. B. C. 7,000. 


3.30 p. m. 
Hb. 84%. 
7.45 p. m. 
Hb. 75%. 


7.30 p. m. 
Hb. 72%. 






•1877 






31 


Hysteromvomectom.v. 
Double S.O. 
Appendectomy. 


2/9/16. 
11.00 a. m. 


Slight. 


2/8/16. 

Hb. 80%. 

W. B. 0. 7,600. 


6.45 p. m. 

Hb. 95%;. 


8.30 p. m. 
Hb. 95%. 


7.45 p. m. 
Hb. 807f. 


7.46 p. m. 
Hb. 807c. 


21878 






42 


Appendectomy. 


2/8/16. 


Slight. 


2/7/16. 

Hb. 83%. 

W. B. C. 15,600. 


8.00 p. m. 
Hb. 85%. 


6.45 p. m. 
Hb. 83%. 


8.15 p. m. 
Hb. 85%. 


7.40 p. m. 
Hb. S37c. 


21888 




White. 


26 J 


Suspension of uterus. 
.\ppciuiectomy. 
D. and C. 
R. R. V. 0. 


2/10/16. 
9. 30 a. m. 


Slight. 


2/9/16. 

Hb. 95%. 

W. B. C. 6,440. 


8.00 p. m. ■ 
Hb. 101%. 


7.30 p. m. 
Hb. 103%. 


7.30 p. m. 
Hb. 99%. 


7.30 p. m. 
Hb. 937c. 


21891 






16 


D. and C. 


2/29/16. 
8.20 a. m. 


Very 

. Slight. 


2/18/16. 
Hb. 90%. 


1.00 p. m. 
Hb. 101%. 
7.45 p. m. 
Hb. 95%. 


8.00 p. m. 
Hb. 100%. 


7.15 p. m, 
Hb. 90%. 


7.45 p. m. 
Hb. 937c. 


21013 




Black. 


38 


Hysteromyomectomy. 
Appendectomy. 


2/23/16. 
9.45 a. m. 


Slight. 


2/22/16. 

Hb. 40%. 

W. B. C. 11,800. 

2/23/16. 9.00 a. m. 

Hb. 38%,. 


11.00 a. m. 
Hb. 34%,. 
9.00 p. m. 
Hb. 44%. 


7.15 p. m. 
Hb. 48%. 


8.00 p. m. 
Hb. 41%,. 


7.45 p. m. 
Hb. 437c. 


21014 






41 


Hysteromyomectomy. 
Double S. 0. 
Appendectomy. 


2/14/16. 
9.20 a, m. 


Slight. 


2/8/16. 

Hb. 53%. 

W. B. C. 5,400. 


12.00 Noon 
Hb. 67%;. 
7.15 p.m. 

Hb. 68%;. 




7.30 p. ni. 
Hb. 667c. 


8.00 p. m. 
Hb. 50';c 






White. 


34 


Hysterectomy. 
Double S. 0. 


2/8/16. 
10.45 a. m. 


Slight. 




8.15 p. m. 
Hb. 88%. 




9.00 p. m. 
Hb. 85%-. 








21939 






19 


Dilatation of cervix. 
Appendectomy. 
Suspension of uterus. 


2/29/16. 
8.45 a. m. 


Slight. 


2/28/16. 
Hb. 93%. 
W. B. C. 9,920. 


1.00 p. 111. 
Hb. 103%;. 
8.00 p. m. 
Hb. 90%;. 




7.00 p. m. 
Hb. 88%. 


8.00 p. m. 
Hb. 907c. 


21940 






31 


D. and C. 


3/14/16. 
8.20 a. ni. 


Very 
Slight. 


3/12/16. 
Hb. 86%. 


8.30 p. m. 
Hb. 91%. 


8.15 p. m. 
Hb. 90%. 






21841 






32 


Dilatation of cervix. 
Cauterization of cervix. 


2/5/16. 
9.45 a. m. 


None. 


2/4/16. 7.15 p. m. 
Hb. 97%. 


7.15 p. m. 
Hb. 100%. 


7.30 p. m. 
Hb. 100';-,. 


7.30 p. m. 
Hb. 1029V. 


7.15 p. m. 
Hb. 105%. 


22002 






3S 


Double salpingectomy. 
Ligation of ovarian and 
internal iliac arteries. 
Percy cautery. 


3/14/15. 
2.00 p. m. 


Verv 
Slight. 


3/13/16. 
Hb. 80%;. 


8.30 p. m. 
Hb. 80-;^. 


8.15 p.m. 
lib. S0%. 


5.45 p. m. 
Hb. 75%.- 




22073 






65 


Lett S. 0. 


4/18/16. 
12.10 p. m. 


Slight. 


4/17/16. 

Hb. 102%. 

W. B. C. 11,000. 


8.00 p. m. 
Hb. 106%. 


S.15 p. m. 
Hb. 108%. 




8.16 p. m. 
Hb. WWc- 


22082 






35 


Hysteromyomectomy. 
Hemorrhoidectomy. 


4/17/16. 
11.00 a.m. 


Slight. 


4/13/18. 

Hb. 110%, 

W. B. C, 8,000. 


9.00 p. ni. 
Hb. 125%. 


7.45 p. m. 
lib. 12Kt. 


9.00 p. m. 
Hb. 125%. 




22023 






24 


Left Salpingectomy. 


3/29/16. 
9.80 a. ni. 


Verv 
Slight. 


3/28/16. 
Hb. 83%). 
W. B. C. 9,160. 


7.30 p. m. 
Hb. 83%. 




8.30 p. m. 
Hb. 82%. 








Black. 


21 


Double salpingectomy. 
Appendectomy. 


1/13, Hi. 
10.00 a. m. 


VlTV 

Slight. 


1/12/16. 
Hb. 89%. 
W. B. C. 8,000. 




Noon. 
Hb. 05%. 


7.00 p. m. 
Hb. 70%. 


7.00 p. m. 

Hb. 727c. 

W. B. C. 18,01 






21831 




While. 


18 


Appendectomy. 


1/22/16. 
9.30 a. m. 


Verv 

Slight. 


1/20/16. 
Hb. 837o. 
W. B. C. 10,120. 


7.00 p. m. 

Hb. 94%;. 


7.30 p. m. 
Hb. 95%. 


7.30 p. m. 
Hb. 95%,. 


7.15 p. m. 
Hb. 987c. 


21862 




Black. 


34 


Hysteromyomectomy. 


1/20/16. 
8.60 a. m. 


Slight. 


1/19/16. 
lib. 74%. 
W. B. C. 4,000, 


8,00 p. m. 
Hb. 77%. 


7,00 p. Ill, 
lib. 78%. 


7.00 p. m. 
Hb. 76%. 


8.00 p. m. 
Hb. 74%. 


21947 




" 


34 


Hysteromyomectomy. 
Appendectomy. 


1/15/16. 
9.00 a. m. 


Slight. 


1 13 16. 
Hb. 75%. 
W. B. C. 15,600. 


7.00 p. m. 
Hb. 86%. 


7.00 p. m. 
lib. 77%. 


7.00 p. ni. 
Hb. 72%. 


8.15 p. m. 
Hb. 69',;. 


21974 






36 


Hysteromyomectoiay. 
Double salpingectomy. 
Left oophorectomy. 
Appendectomy. 


3/14/18. 
Noon. 


Slight. 


8/13/16. 
Hb. 92%. 
W. B. C. 13,000. 


7.30 p. m. 
Hb. 83%. 


7.45 p, m. 
lib. 79%. 


5.30 p. m. 
Hb, 83%, 




22031 




White. 


47 


Hysteromyomectomy. 
Double S. 0. 
Appendectomy. 
R. R. V. 0. 


3/27/16. 
Noon. 


Slight. 


2,15/16. Hb. 40%;. 

R. B. C. 2,352,000. 

W. B.C. 1,000. 

3/22/16. Hb. 50%. 

R. B. V. 3,800,000. 

W. B. r. 1,100. 
8/26/16. 2 p.m. Hb. 64%. 
3/27/16. Noon, lib. .■;3% 


1.30 p. m. 
Hb. 64%. 
8,46 p. m. 
Hb. 68%. 

1 




9.00 p. m. 
Hb. 63%. 





























AXUAKY, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



19 



TABLE I.— HAEMOGLOBIN IN" CASES WITH VERY SLIGHT BLOOD LOSS AT OPERATION 



■2/6/16. 
11.00 a. II 
Hb. 91</t. 



2/24/16. 
7.45 p. m. 
Hb. 75%. 

2/24/16. 
7.30 p. m 
Hb. 76%. 

2/27/16. 
7.45 p. 111. 
Hb. 'J2%. 



3/7/16. 
7.45 p. m. 
Hb. 48%. 



2/27/16. 
7.30 p. 111. 
Hb. 61%. 



2/26/16. 
8.30 p. m, 
Hb. 83%. 



5/5/16. 
8.00 p. m. 
Hb. 112%. 
R. B. C. 
6,120,000. 



1/28/16. 
Noon. 
Hb. 79%. 



Fluids Taken. 
Vomiting 



3/10/16 
10.30 a. m, 
Hb. 68%. 



Water well taken after 

operation. 
No vomiting. 



Water not well taken after 

operation. 
Slight vomiting. 



20 






> 


JOHNS 


HOPKINS HOSPITAL 


BULLETIN 




[No. 32: 






TABLE II.— HAEMOGLOBIN IN CASES WITH MODERATE BLOOD LOSS 




Oyn. 

No. 


Female 


Race 


Age 


Operation 


Date 


Blood Loss of 
Operation 


Before 
Operation 


After 
Operation. 

Day of 
Operation 


2d Day 


3d Day 


4th Day 


21647 


" 


White. 


39 


Curettage and cauterization of 
cervix. 


11/2/15. 
9.45 a. m. 


Moderate. 


11/1/15. 
Hb. 629i. 




Noon. 
Hb. 577,. 


Noon. 
Hb. 547c. 














14 


D. and C. 


1/20/16. 
8.20 a. m. 


Moderate. 


1/19/16. 
Hb. 357c. 




Noon. 
Hb. aO'A. 


Hb. 31%. 


7.45 p. m. 
Hb. 287c- 












39 


Dilatation of cervix and man- 
ual removal of placenta. 


11/25/16. 
8.45 p. m. 


Very slight. 

See 
"Remarks." 


11/25/16. 

8.30 p. m. 

Hb. 617c. 

W. B. C. 15,500. 

R. B. C. 3,880,000. 




7.45 p. m. 

Hb. 537,. 

R. B. C. 3,600.000. 




7.46 p. m. 

Hb. 52%. 

W. B. C. 9,»00. 

R. B. C. 3,900,000 








21876 






30 


D. and C. 
R. R. V. 0. 


2/8/16. 
8.20 a. m. 


Moderate. 


2/7/16. 

Hb. 967,. 

W. 13. C. 1?,520. 


7.45 p. m. 
Hb. 947,. 


7.00 p. m. 
Hb. 86%. 


8.00 p. m. 
Hb. 827c. 


7.15 p. m. 
Hb. 82%. 


21879 


" 


•' 


19 


Hysterectomy (bi-section). 
Double salpingectomy. 
Right oophorectomy. 


2/10/16. 
11. .W p. m. 


Moder'ate. 


2/9,-10. 

Hb. 93-/;. 

W. B. ('. 8,200. 


S.45 p. m. 
Hb. 867c. 


8.00 p. m. 
Hb. 8.17c. 


7.45 p. m. 
Hb. 7571. 


S.OO p. m. 
Hb. 707c. 


21931 






3C 


Hysteromyomectomy. 
Double salpingectomy. 
Appendectomy. 
Anterior and posterior colpor 
rhaphy. 


2/26/16. 
11.25 a. m. 


Moderate. 


2/25/10. 

Hb. 677,. 

W. B. C. 9,400. 


2.00 p. m. 
Hb. 627,. 
i hr. after op. 
7.45 p. m. 
Hb. 577f. 


7.00 p. m. 
Hb._ 547c. 


8.00 p. m. 
Hb. 507c. 


7.15 p. m. 
Hb. 46%. 


210!I3 






33 


Hysteromyomectomy. 
Rt. salpingectomy. 
.\ppendectomy. 


2/29/16. 
a. m. 


Moderate. 


2/28/16. 

Hb. 867;. 

W. B. C. 8,000. 


1.50 p. m. 
Hb. 767c. 
7.30 p. m. 
Hb. 807c. 


7.45 p. m. 
Hb. 847c. 


6.45 p. m. 
Hb. 777c. 


7.00 p. m. 
Hb. 70%. 


22046 




'■ 


47 


Amputation cervi.v. 

R. K. V. 0. 

Cauterization fissure in aiio. 


3/14/16. 
8.45 a. m. 


Moderate. 


3/13/10. 

Hb. 867,.. 

W. B. C. 5.360. 


8.00 p. m. 
Hb. 767,. 


8.00 p. m. 
Hb. 7<y/r. 


6.00 p. Hi. 
Hb. 72%. 








22128 






23 


D. and C. 

Posterior vaginal coliolomv. 

Resection of left ovary. 


5/13/16. 
10.20 a.m. 


Slight. 

See 

" liemarks." 


5/13/10. 

10.20 a. ni. 

lib. 1007. 

W. li. C. 9,.i00. 


8.00 p. m. 
lib. 1007,. 


8.00 p. m. 
Hb. 807c. 




9.00 p. m. 
Hb. 88%. 






20883 






20 


Panhysterectomy. 
Double salpingectomy. 
Left oBphorcctomy. 


1/25/lS. 
a. m. 


Slight. 

1/25/15. 

Hiemorrhage on 

ward. 


Not made. 


2/6/15. 

8.00 p. m. 

Hb. 657c. 

6.00 p. m. 

Severe bleeding. 


a.00 p. m. 

Hb. 38%. 

Very little blecd- 

. ing. 


Hb. 85%j- 
No bleeding. 


Hb. 39%. 
No bleeding. 


20009 


" 




21 


D. and C. ca\iter'ization cervix. 
R. R. V. 0. 
Hemorrhoidectomy. 


1/28/15. 


Slight. 

2/B/16. 

6.00 p. m. 

Severe blemor- 

rhage. 


Xol nnule. 


2/0/15. 
8.30 p. m. 
Hb. S07,!. 
10.30 p. m. 
lib. 707c. 


Noon. 

Hb. 707c. 

No bleeding. 


10.00 a. m. 

Hb. 657c. 

No bleeding. 


Hb. 53%. 
No bleeding. 



Fanuaey. 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



21 







TABLE II.— H.'Eli 


lOGLOI 


.IN IN CASES 


WITH MODERATE BLOOD LOSS 




5th Day 


6th Day 


7th Day 


8tb Day 


9th Day 


lOth Day 










Fluid Taken. 
Vomiting 


Remai^lis 


Noon. 


8.30 p. m. 
Hb. 60%. 






8.30 p. m. 
Hb. 54%. 




11/12/15. 
Hb. 58%,. 













Hb. 48%. 












Hb. 42%. 
















Pt. had constant bleeding for 
2 mos. due to endometrial hy- 
perplasia. 


Hb. 34%. 
R. B. C. 
3,864,000. 
























Water well taken after opera- 
tion. 
No vomiting. 


Began to bleed 2 days before op. 
Profuse hemorrhage 5 hns. be- 
fore op. 


T.15 p. m.- 
Hb. 777c. 


7.30 p. m. 
Hb. 75%>. 


8.00 p. m. 
Hb. 73%,. 


7.00 p. m. 
Hb. 71%. 






2/19/16. 
8.15 p. m. 
Hb. 80%. 








Considerable vomiting day 
after operation. 






7.15 p. m. 
Hb. 73%. 




7.45 p. m. 
Hb. 74%. 








2/22/16. 
7.45 p. m. 
Hb. 71%. 










- 


7.30 p. 111. 
Hb. 46?',,. 




7.30 p. m. 
Hb. 50%. 








3/7/16. 
7.30 p. m. 
Hb. 54%,. 


3/26/16. 
7.30 p. m. 
Hb. 52%. 






Salt sol. 300 c. c. p. r. q. 4 h. 
day of operation. 








8.30 p. m. 
Hb. 80';,. 




8.00 p. m. 
Hb. 78%. 






3/15/15. 
7.45 p. m. 
Hb. 80%. 


















8.00 p. m. 
Hb. 69%. 
W.B.C.7,800. 






8.00 p. ra. 
Hb. 70%. 














Some vomiting for 2 days. 
Post op. 






8.45 p. m. 
Hb. 88%,. 




7.45 p. m. 
Hb. 90%. 
















Verv little vomiting. 
Post op. 


Pt. says she had hemorrhage 
night of 5/12/16 and mornine 
of 5/13/10. 


lU.llll a. ni. 

Severe 
bleeding. 
8.00 p. m. 
Jib. 41%,. 


S.OO p. 111. 
Hb. 30%. 

No 
bleedinff. 


4.00 p. m. 

Hb. 209'f, 
K. B. C. 

1,200,000. 
No bleed'g. 


7.00 p. m. 
Hb. 24%. 

No 
bleeding. 




2/16/15. . 
5.00 p. m. 
Hb. 30%. 

No 
bleeding. 


2/19/15. 
4.00 p. m. 
Hb. 22%^. 

No 
bleeding. 


2/23/15. 
Hb. 12%. 
2/20/15. 
H.-emor- 
rhage. 


2/26/15. 
Hb. 18%. 

No 
bleeding. 


2/28/15. 
Hb. 25%. 

S 2/15. 
Hb. 35%. 
N-o bleed'g. 


2/12/15. 

Indirect transfusion 300 c. e. 

2/22/15. 

Salt sol. infusion. 


Hemorrhage was from a small 
vessel in vaginal vault. 


Hb. 46%. 

No 
bleeding. 


Hb. 50%. 

No 
bleeding. 






Profuse 
haemor- 
rhage. 


2/19/15. 
Hb. 64%. 


2/21/15. 
Hb. 68%. 








2/8/15. 
Salt .sol. infu.'iion 6IKI c. c. 


Bleeding began 6/4/15. Not 
scvercuntil6/6 15 at 6.00 p.m. 



22 



JOHNS HOPKINS HOSPITAL BULLETIN 



TABLE III.— H^MOGLOBIX IN CASES OF SEVEEE H^^MOERHAGE 



22593 




21160 


•■ 


21321 


'■ 



Dilatation and curet- 
tage. 
Rt. S. O. 



21 Resection of left tube. 




Double sapingectomy. 



Panhvsterectun 
Left S. O. 
R. R. V. O. 

Hysteromyomec 
Right S. 0. 
.\ppendectomy. 



Pelvic puncture. 
Exploratory laparot- 
omy. 



11/15/15. Severe 

11.00a.m. b.xmor- 

1 rhage. 



2/16/16. I Severe 

Noon. h;pmor. 

rhage. 



3/8/16. 
11.50 p. m 



4/1/6. 
12.45 p. n 



.V22/16. Severe 

10.30 a. 

rhage. 



11/4/16. Profuse 

8.40a. in. hirmor- 

rhage. 



Profuse 
li.Tmor- 
rhage. 



Slight. 

See 

'Remarks' 




11/30/14. 1 a. m. 

Hb. 70%. 
W. B. C. 20,000. 

12/2/16. 9 p. m. 

Hb. 56%. 

W. B. C. 10,600. 

R. B. C. 3,950,000. 



6/19/16. 

Hb. 82%. 

\V. B. C. 9,100. 



. 12/17/15. 
Hb. 61%. 
W. B. C. 13,600. 



2/15/16. 

Hb. 73%. 

W. B. O. 21,600. 



3/11/16. 

Hb. 80%. 

W. B. C. 7.200. 



3/7/16. 
Hb. 49%. 
W. B. C. 12,800. 

3/31/16. 

Hb. 72%:. 

W. B. C. 7,200. 

2/1/16. 

Hb. 40%. 

\V. B. C. 0,200. 

R. B. C. 2.160,000. 

2/15/lb. 

Hb. 40%. 

W. B. C. 1,600. 

R. B. C. 2,352,000. 

5/'22/16. 

Hb. 49%. 

W. B. C. 14,200. 

6/15/16. 
I Hb. 95%. 
I W. B. C. 19,000. 
5/16/16. 5 p. m. 

Hb. 96%. 

5/21/16. 

Hb. 70%. 

W. B. C. 8,920. 

5/30/16. 

Hb. 85%. 

6/12/16. 4.00a.m. 

Hb. 51%. 



Atter 
Operation. 

Day of 
Operation 



3.00 p.m. 

Hb. 50%. 

W. B. C. 12,000. 

11.00 p. m. 

Hb. 50%. 

W. B. S. 20,000. 

R. B. C. 4,'200,000. 



10.30 a. m. 

Hb. 70%. 

W. B. C. 7,600. 

R. B. C. 4,352,000. 



Hb. 83%. 
7.30 p. m. 
Hb. 72%. 

1.00 p. m. 
Hb. 76%. 
9.00 p. m. 
Hb. 68%. 



Noon. 
Hb. 38%. 
7.30 p. m. 
lib. 28%. 



2.00 p. m. 
lib. 45%. 
7.30 p. m. 
Hb. 3S%. 

2.00 p. m. 
Hb. 95%. 
9.00 p. m. 
Hb. 92%. 



1.00 p. m. 
Hb. 70%. 
7.15 p. m. 
Hb. 60%. 

4.30 a. m. 
Hb. 51%. 
8.00 p. m. 
Hb. 43%. 



11/2/16. i hr. after opera- 

Hb. 68%. tion. 

W. B. C. 8,700. Hb. 76%. 

IR. n. r. 4,240,000. 



5/5/15. 

Hb. 80%. 

\V. B. C. 6,700 

,6/29/15. 2.00p.ni. 
! Hb. 63%. 

7.15 p. m. 

Hb. 45%. 
6/30/15. 10.46a.m. 

Hb. 47%^ 



11.30 a. m. 
Hb. 40%. 
R. B. C. 

2,440,000. 



9.30 p. ra. 
Hb. 122%. 



4.30 p. m. 

Hb. 55%. 
W. B. C. 11,600. 
R. B. C. 

3,400,000. 



Hb. 34%. 



12.30 p. m. 
Hb. 30%. 
R. B. C. 

1,936,000. 



9.00 p. m. 
Hb. 49%. 
R. B. C. 

3,268,000. 



3.00 p. m. 

Hb. 25%. 

W. B. C. 2,320. 



Hb. 40%. 



12.30 p. m. 

Hb. 27%. 

R. B. C. 2,120,000. 



8.00 p. m. 
Hb. 98%. 
W. B. C. 9,000. 
R. B. C. 5,000,000. 
Difl'erential nor- 
mal. 



11.00 a. m. 

Hb. 39%. 

R. B. C. 2,432.000. 



7.30 p. n 

Hb. 24^ 

R. B. C. l,9t 



rANUAEY. 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



23 



TABLE III.— HEMOGLOBIN IN CASES OF SEVERE HiEMOERHAGE 



6th Day 7th Day 8th Day 9th Day 10th Day 



7.15 p. m. 
Hb. 657c. 



Hb. t%%. 
R. B. C. 

2,300,000. 



9.15 p.m. 
Hb. 52%. 
R. B. C. 
3,680,000. 



4.30 p. m. 
Hb. 43%. 
J. B. C. 
3,3J8,000. 



8.30 p. m. 
Hb. 95%. 



Hb. 377c. 



8.00 p. m. 
Hb. 25%. 
R. B. C. 

1,368,000, 



Hb. 37%. 
W. B. C. 
13,000. 



7.30 p. m. 
Hb. 60%. 



Hb. 707o. 



12/16/16, 
11.00 a. ra 

Hb. 42%, 
W.B.C.8,200 



11/26/15. 
11.45 a. m. 
Hb. 95%. 



2/27/16. 
r.30 p. m. 
Sb. 587c. 



4/11/16. 
5.00 p. m. 
Hb. 587c. 



8,200. 
R. B. C. 
1,228,000. 



6/23/16. 

Noon. 
Hb. 56%. 



11/14/16. 
11.45 a. m. 
Hb. 467c. 
W. B. C. 

15.800. 
R. B. C. 
3,208,000. 
5/21/15. 
lb. 76%. 



3/3/16. 
7.30 p. m. 
Hb. 60%. 



3/21/16. 
Hb. 42%. 



6/29/16. 
8.35 p. m. 
Hb. 53%. 



7/16/15. 
Hb. 427c. 



3/23/16. 3/26/16. 
Hb. 527c. Hb. 527c. 
3/30/16. 
Hb. 62%,. 



7/27/15. 
Hb. 50%. 

7/19/15. 
Hb. 42%. 



Blood not removed fro 
cavity at operation. 



Infusion of salt sol. 1000 c. c. 
begun at op. Water taken 
greedily after op. No vomi* 
ting. 

Infusion of salt sol. 1500 c. c. 
begun at. op. Water taken 
well after op. Very little 
vomiting. 



Infusion of salt sol. 2500 c. ( 
begun at op. 1 litre of sal 
sol. left in abd. cavity at en 
of op. No vomiting. 



Ruptured tubal pregnancy 
Abd. full of blood at op. Onset 
1/5/03. 

Ruptured tubal pregnancy. 
Ab. full of blood at op. Onset 
8/16/03. 

Ruptured tubal preenancv. 
About 2 litres blood in abd. 
Onset 12 hrs. before op. 

Ruptured tubal pregnancv. 
Onset about 36 hrs. before oi) 
Abd. filled with fresh blood. 



Tubal pregnancy ruptured ) 
hr. before op. under ether. 
About 2 litres of fresh blood 
in abd. at op. 



Tubal pregnancy 
about 36 hrs. befor 
timated 600 c. c. bio 
at op. 



Salt sol. infus 



Salt sol. infus: 



Died 6/1/16 from general per 



Salt sol. infusion 2500 c. 
gun at op. 



. be- Bleeding began 6/11/16. 3.S0 
p. m. Severe haemorrhage 
6/12/16 1.00 a. m. pack ne- 
placed. 



Salt sol. infusion 840 c. c. on 
table. Salt sol. p. r. 1200 c. c. 
1st IS hps. No vomiting. 



Salt sol. infusion on table 700 
c. c. Salt sol. p. r. 300 c. c. 
q. 4 h. onward. 



Salt sol. infusion 900 c. c. be- Some bleeding for 2 weeks 
gun at op. Took water eager- Severe ha'morrhage 7.45 a. m 
ly after op. ' 6,30/15. 



* tf-0 

V 

10 






XI 



TTT 



ffl 



;| f i :i i i t 

' 1 1 ! : I i 



J_i- 






-i8-4- 









••f-f-4-h-t- 







11 IlII Jlil 



J_l_!_l 

1 i I Y" 



4_j....j_i-i....l..-.i...j_I...LJ_l~.i.-i_.]- 



i I I 



I ! ! ! 



Chart I. — Hemoglobin curves in cases of very slight blood loss. 






5 

o 
5 70 








i 



30 



I I I 



T:t:i:t:i::ij..j..j,...i....u„i,j.. 

XX.X j..._i._i_i...J._.i._.i.._.L.L4....1.. 

. l_.i.J_J_|_UU....U--L-..i.-l.. 

, ^.;.__j — \ — J — .....*_..,...-.^ — r-~t— •■! — •;•■ 

t1 5...jf...i*..l i i....L.i i....i...lJ.. 

:|lrii:.L.l.jJ i i U 

|r:,:tJ::i;i:]:n:n:]:n 
Jliiti t rt] 1 [■■*•[ 

! 1 1 I I i 1 t ! ' 1 



1 1 • 
..I..4..-I. 




..i..-.5...-f. 
IIII 



..|...A.i. 



.4.4... 

liii: 



..L.. .' 




I _ j j....].._i__i.... i ..i....i J 






Chart III. — Hemoglobin curves in cases of severe hemorrhage. 



^^tH)i 



pit 
Hd: 



i J i I |..-.i i.-i l-X-X i i5^i 

iilijJ-lili'iillil ' 
t"-] r"i""p"]- j i -|- j •-|™~»-|----.~Y~ .-.-1 

' ' ' ' ""' i:i:iii:.i..j::Li:ij::i:t 

i.....i.J i-..-...l....!...,i.J„i_i.....l.J_L..l..._L...l.„i. 

I 1 i ! ! I i ■ 



-H l-i 



.J._IJ 



]iiiiii-jiiizii|zX'l-i-i-i--ii-ri 

!! ii liTir"! til r i'T'i 



4..-.i.4-..a.. 



i— .— i 4 * 4-.4-.-4.....4..-.4-.-4 — U..4 — i— i.....i — i..-.4-_4 

I I I 1 I I I i I II I I i I ! i i i 




'. . .hernorrhoA 

1 'T ij' 1 T i .'. i i..J 



1 I 1 I ! 1 ! —iJ- 



Chakt II. — Hemoglobin curves In cases of moderate blood loss. 



Chart IV. — Hemoglobin curves in cases of slight, moderate ani 
severe hemorrhage. 



January, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



25 



MEMBERS OF THE JOHNS HOPKINS HOSPITAL AND DISPENSARY 
STAFF ENGAGED IN MILITARY DUTY 



De. William H. Welch, Major, M. O. R. C, special duty, Surgeon 
General's Office. 

De. Winfobd Smith, Major, M. O. R. C, special duty. Surgeon Gen- 
eral's Office. 

Db. Theodoee C. Janeway, Major, M. 0. R. C, special duty, Sur- 
geon General's Office. 

Db. William S. Thateb, Major, M. 0. R. C, Red Cross Commission 
to Russia. 

Db. John M. T. Finney, Major, M. 0. R. C, Cliief of Surgical Staff, 
U. S. Army Base Hospital No. 18, American Expeditionary 
Force, France (Hopkins Base Hospital). 

Dr. Thomas R. Boggs, Major, M. O. R. C, Chief of Medical Staff, 
U. S. Army Base Hospital No. IS, American Expeditionary 
Force, France (Hopkins Base Hospital). 

Dr. George Walker, Major, M. O. R. C, Adjutant and Surgeon, 
U. S. Army Base Hospital No. IS, American Expeditionary 
Force, France (Hopkins Base Hospital). 

Dr. Hugh H. Young, Major, assigned to Britisli medical service. 

Dr. Thomas B. Futcher, Consultant, Canadian Military Hospital, 
B. E. F., Orpington, Kent, England. 

Dr. William S. Baer, Captain, M. O. R. C, Assistant Surgeon, (Or- 
thopedic) U. S. Army Base Hospital No. IS, American Ex- 
peditionary Force, Prance (Hopkins Base Hospital). 

Dr. F. H. Baetjer, Major, M. 0. R. C, on active duty, Johns Hop- 
kins Hospital. 

Dr. Clyde G. Guthrie, Captain, M. 0. R. C, Assistant Physician, 
U. S. Army Base Hospital No. 18, American Expeditionary 
Force, France (Hopkins Base Hospital). 

Dr. George J. Heuer, Captain, M. O. R. C, Assistant Surgeon 
(Brain Surgery), U. S. Army Base Hospital No. 18, Ameri- 
can Expeditionary Force, France (Hopkins Base Hospital). 

De. Walter A. Baetjer, Captain, M. 0. R. C, Chief of laboratory 
staff, U. S. Army Base Hospital No. IS, American Expedition- 
ary Force, France (Hopkins Base Hospital). 

Dk. Charles Bagley, Captain, M. 0. R. C, assigned to duty in Sur- 
geon General's Office. 

Dr. Bertram M. Bernheoi, Captain, M. 0. R. C, Assistant Sur- 
geon (Vein Surgery), U. S. Army Base Hospital No. IS, 
American Expeditionary Force, France (Hopkins Base 
Hospital). 

De. Eveletii W. Bridgmax, Captain, M. O. R. C, Assistant Phy- 
sician and Registrar, U. S. Army Base Hospital No. IS, 
American Expeditionary Force, France (Hopkins Base Hos- 
pital). 

Dr. John Staige Davis, Captain, M. 0. R. C, on active duty, Bal- 
timore. 
Dr. William A. Flsher, Captain, M. O. R. C, Assistant Surgeon, 

U. S. Army Base Hospital No. 18, American Expeditionary 

Force, France (Hopkins Base Hospital). 
Db. Harvey B. Stone, Captain, M. 0. R. C, Quartermaster, U. S. 

Army Base Hospital No. 18, American Expeditionary Force, 

France (Hopkins Base Hospital). 
Dr. Stanhope Bayne-Jones, Captain, M. 0. R. C, U. S. Army 

Medical Relief Corps, France. 
DB; David M. Davis, 1st Lieutenant, M. O. R. C, on active duty in 

France. 



Dr. H. C. Schmeisseb, 1st Lieutenant, M. 0. R. C, Pathologist, 
Albany Base Hospital. 

Db. J. Albert Ciiatard, 1st Lieutenant, M. O. R. C, on active 
duty, Fort McHenry. 

Db. J. A. C. Colston, 1st Lieutenant, M. 0. R. C, on active duty. 
Medical Department, British Army in France. 

Dr. Frank A. Evans, 1st Lieutenant, M. 0. R. C, on active duty, 
Medical Department, British Army in France. 

Db. John H. King, 1st Lieutenant, M. 0. R. C, Assistant Physician, 
U. S. Army Base Hospital No. IS, American Expeditionary 
Force, France (Hopkins Base Hospital). 

De. J. H. M. Knox, Jr., Red Cross Commission to France. 

De. E. a. Park, Red Cross Commission to France. 

Dr. John T. King, Jb., 1st Lieutenant, M. 0. R. C, on active duty, 
assigned to J. H. H. 

Dr. Willi,\m L. Millea, 1st Lieutenant, M. 0. R. C, on active duty. 
Camp Oglethorpe, Ga. 

Db. Henry R. Slack, 1st Lieutenant, M. 0. R C, Assistant Surgeon 
(Laryngology), U. S. Army Base Hospital No. 18, American 
Expeditionary Force, France (Hopkins Base Hospital). 

Dr. Henry L. Smith, 1st Lieutenant, M. O. R. C, on active duty, 
Fort Oglethorpe, Ga. 

Dr. Daniel D. V. Stuakt, Captain, M. 0. R. C, on active duty, 
Washington, D. C. 

Dr. George L. Stickney, 1st Lieutenant, M. 0. R. C, on active duty. 
Medical Department, British Army in France. 

Dr. Alan C. Sutton, 1st Lieutenant, M. 0. R. C, on active duty. 
Medical Department, British Army in France. 

Dr. Charles A. Waters, 1st Lieutenant, M. O. R. C, Roentgenol- 
ogist, U. S. Army Base Hospital No. 18, American Expe- 
ditionary Force, France (Hopkins Base Hospital). 

Db. Clarence A. Neymann, 1st Lieutenant, M. 0. R. C, New York 
Psychiatric Unit. 



Former members of the Hospital and Dispensary Staff who 
resigned during the past year to take up active military duty: 
Dr. D. C. W. Smith. 



Db. Everett D. Plass. 

Dr. Daniel Davis. 

Dr. Aubrey T. Mussen. 

Db. John C. Lyman. 

Db. Raymond S. Hussey. 

Dr. Virgil P. W. Sydenstrickeb, 

Dr. H. N. Shaw. 

Db. L. R. Wharton. 

Dr. Charles L. McCarthy. 

Dr. Howard E. Asiihury. 

Db. Ernest S. du Bray. 

Dr. George R. Dunn. 

Dr. J. p. Edison. 

Dr. R. W. Hall. 

Dr. W. D. Jack. 

Db. U. R. Mason. 

Dr. T. L. Sutton. 

De. C. E. Seviee. 

Db. D. G. Smith. 

Dr. H. C. Schmeisseb. 



Dr. H. W. Reid. 

Dr. J. E. Moobe. 

Dr. M. K. Millee. 

Dr. P. F. McGuiee. 

Dr. L. K. McCafferty. 

Dr. W. B. Martin. 

Dr. I. K. Lovett. 

Db. J. A. Etheridge. 

Dr. H. C. Bean. 

Dr. Lawrence Reynolds. 

Db. G. a. Stewart. 

Dr. Ro.ides Fayerweatheb. 

Db. L. C. Spenceb. 

Dr. Elizabeth Hurdon. 

De. H. L. Cecil. 

Db. N. M. Keith. 

De. G. H. Preston. 

Dr. N. Worth Brown. 



26 



JOHNS HOPKINS HOSPITAL BULLETIN 



[Xo. 323 



NOTES AND NEWS 



Dr. Dana W. Atchley is Instructor in Medicine and Instructor in 
Clinical Pathology, College of Physicians and Surgeons, Colum- 
bia University, New York City; and Assistant Physician, Presby- 
terian Hospital. 

Dr. Frank C. Beall is Surgeon-in-Charge, the Johnson-Beall Hos- 
pital, Fort Worth, Texas. 

Dr. Barney Brooks is Associate in Surgery, Washington Univer- 
sity Medical School, and Visiting Surgeon, Barnes Hospital, St 
Louis, Mo. 

Dr. S. W. Budd is Associate Professor of Pathology and Asso- 
ciate in Medicine, Medical College of Virginia, Richmond, Va. 

Dr. Walter C. Burket is First Lieutenant, Medical Reserve 
Corps. He is at present with Field Hospital No. 19, which is sta- 
tioned at Fort Riley, Kansas. 

Dr. Montrose T. Burrows is Associate Professor of Pathology 
and Acting Professor of Pathology, Washington University Medi- 
cal School, St. Louis, Mo. 

Dr. C. N. B. Camac is a Major in the Medical Reserve Corps, and 
Medical Chief of the Base Hospital. Fort McPherson, Ga. He is also 
Instructor in the School of Gas Defense, United States Army. 

Dr. John R. Caulk is Associate in Clinical Genito-Urinary Sur- 
gery, Washington University; Assistant Surgeon to Barnes Hos- 
pital; Chief of Clinic, Genito-Urinary Department, Washington 
University Dispensary; Genito-Urinary Surgeon to St. Luke's 
Hospital, St. Louis, Mo. 

Dr. John W. Churchman is Professor of Surgery. Vale Uni- 
versity; Visiting Surgeon, New Haven Hospital; Acting Head of 
the Department of Surgery; Acting Chief Surgeon, New Haven 
Hospital and New Haven Dispensary. 

Dr. S. W. Clausen is Resident Physician, Children's Hospital, St. 
Louis, Mo. 

Dr. Henry Wireman Cook is Assistant in Medicine, the Uni- 
versity of Minnesota. 

Dr. C. D. Cowles, Jr., is Major in the Medical Corps, U. S. A., 
and Is stationaed at Fort Oglethorpe, Ga. 

Dr. Arthur W. Elting is Major in the Medical Reserve Corps and 
Director of Base Hospital No. 33. 

Dr. Clarence B. Farrar is Captain in the Canadian Army Medical 
Corps and is connected with the Psychiatric Military Hospital, 
Ottawa, Canada. 

Dr. L. W. Gorham is Instructor in Medicine, Albany Medical 
College, and Assistant Attending Physician, Albany Hospital. He 
is a member of the Medical Reserve Corps and is Chief of Medical 
Service, Base Hospital No. 33. 

Dr. R. L. Haden is Director of Laboratories, Henry Ford Hos- 
pital, Detroit, Mich. 

Dr. C. W. Hennington is Major in the Medical Reserve Corps, and 
Assistant Director and Chief of the Surgical Service, Base Hos- 
pital No. 19. 

Dr. James M. Hitzrot is Assistant Professor of Clinical Surgery, 
Cornell University Medical College. 

Dr. August Hoch is editor of the Psychiatric Bulletin. Address: 
Montecito, Cal. 

Dr. Samuel H. Hurwitz is Assistant Clinical Professor of Medi- 
cine, Medical Department, University of California. 

Dr. Clarence B. Ingrahani is Professor of Gynecology and Ob- 
stetrics, the University of Colorado. He is Captain in the Medical 
Reserve Corps and is stationed at present at Fort Riley, Kansas. 

Dr. Theodore C. Janeway is a member of the General Medical 
Board of Council of National Defense. 



Dr. Harry L. Langnecker is Passed Assistant Surgeon, U. S. 
N. R. F. He is Orthopedist to the Naval Base Hospital Unit No. 2. 

Dr. D. Sclater Lewis is with No. 3 Canadian General Hospital, 
B. E. F., France. 

Dr. Irving P. Lyon is Assistant Professor of Medicine, University 
of Buffalo, and Attending Physician, Buffalo General Hospital. 

Dr. W. G. MacCallum is Professor of Pathology and Bacteriology, 
Johns Hopkins University, and Pathologist to the Johns Hopkins 
Hospital. 

Dr. R. H. Major is Professor of Pathology, University of Kansas, 
Rosedale, Kansas. 

Dr. Kenneth F. Maxcy is a member of the Medical Staff, Henry 
Ford Hospital, Detroit, Mich. 

Dr. William B. McClure is Fellow in the Otho A. Sprague 
Memorial Institute. Chicago, 111. 

Dr. Carl R. Meloy is Director of Laboratories, the Grace Hospital, 
Detroit, Mich. 

Dr. George R. Minot is Assistant in Medicine, Harvard Medical 
School, Assistant in Medicine, Massachusetts General Hospital, 
and holder of flie Dalton Research Fellowship, Massachusetts 
General Hospital. 

Dr. Charles F. Nassau is Assistant Professor of Surgery, Jeffer- 
son Medical College; Chief Surgeon, Frankford Hospital; Surgeon, 
St. Joseph's Hospital; Assistant Surgeon, Jefferson Medical College 
Hospital; and Consulting Surgeon. Pottstown Hospital, Pottstown, 
Pa. 

Dr. C. D. Parfitt is Special Adviser in Tuberculosis, Toronto 
General Hospital. 

Dr. H. W. Plaggemeyer is Instructor in Surgery, Detroit Medical 
College. Chief of Staff, Department of Urological Surgery, Grace 
Hospital, and Junior Attending Surgeon, Harper Hospital, Detroit, 
Mich. 

Dr. J. P. Pratt is Assistant Surgeon, Henry Ford Hospital, 
Detroit, Mich. 

Dr. D. Maxwell Ross is in charge of mental wards, 52d General 
Hospital, B. E. M. F., Salonika. 

Dr. Peyton Rous is Associate Member, Rockefeller Institute for 
Medical Research, New York City. 

Dr. Lewis A. Sexton is Superintendent, the Hartford Hospital. 
Hartford, Conn. 

Dr. W. F. Shallenberger is Associate Professor of Gynecology, 
Emory University (Atlanta Medical College); Visiting Gyne- 
cologist, Georgia Baptist Hospital, and Assistant Visiting Gyne- 
cologist, Grady Hospital, Atlanta, Ga. 

Dr. William Sharpe is Attending Neurologist to the Beth Israel 
Hospital, New York City. 

Dr. Winford H. Smith is a member of the General Medical 
Board of Council of National Defense. 

Dr. R. R. Snowden is a First Lieutenant in the Medical Reserve 
Corps. He is on duty in France with Base Hospital Unit No. 27. 

Dr. A. R. Stevens is a member of the Medical Reserve Corps 
and is with the N. Y. Presbyterian Base Hospital Unit in France. 

Dr. Solomon Strouse is Assistant Professor of Medicine. North- 
western University School of Medicine. 

Dr. Martin B. Tinker is a Major in the Medical Reserve Corps. 
He is stationed at present at Fort Riley, Kansas. 

Dr. Donald V. TVueblood is a First Lieutenant in the Medical 
Reserve Corps, and has been assigned to duty with the American 
Expeditionary Force in France. 



January, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



27 



Dr. P. S. Tucker is First Lieutenant, Medical Corps, U. S. A., 
and is stationed at Fortress Monroe, Va. 

Dr. J. H. J. Lipham is Professor of Medicine and Acting Head 
of tlie Department, Ohio State University Scliool of Medicine, 
and Presio'ent of tlie Oliio State Medical Board. 

Dr K. H. Van Norman is Assistant to Assistant Director Medical 
Services (A. D. M. S!) Military District No. 2; headquarters, 
Toronto. 

Dr. L- M. Warfield is Assistant Superintendent, Milwaukee 
Coi:nty Hospital, Wauwatoso, Wis., and Professor of Clinical Medi- 
cine at Marquette Medical School, Milwaukee, Wis. 

Dr. Ernest M. Watson is Assistant Visiting Urologist to the 
Municipal Hospital and to the Erie County Hospital, Buffalo, N. Y. 

Dr. Charles H. Watt is Surgical Director of the Union Hospital, 
Fall River, Mass. 

Dr. Jerome P. Webster is First Lieutenant Medical Reserve 
Corps, and is stationed at Fort Benjamin Harrison, Ind. 



Dr. William H. Welch is Director of the School of Hygiene to be 
established in connection with the Johns Hopkins University. 

Dr. Milton C. Winternitz is Professor of Bacteriology and Path- 
ology, Yale University School of Medicine, and Pathologist to the 
New Haven Hospital. 

Dr. Paul G. Woolley is Mary M. Emery Professor of Pathology, 
University of Cincinnati. He is a Captain in the Medical Reserve 
Corps, and is stationed at Fort Oglethorpe, Ga. 

Dr. J. Kent Worthington is Assistant in Urology, Indiana Uni- 
versity School of Medicine; Assistant and Attending Urologist, 
City Hospital; and Attending Urologist, City and Babbs Dis- 
pensary. He is a Captain in the Medical Reserve Corps, and is 
stationed at present at Fort Benjamin Harrison, Ind. 

Dr. Charles B. Wright is Chief of the Gastro-Intestinal Clinic, 
University Dispensary, and Assistant Visiting Physician, Uni- 
versity Hospital, Minneapolis, Minn. 



BOOKS RECEIVED 



Diseases of the Genito-Vrinary Organs and the Kidney. By Robert 
Holmes Greene, A. M., M. D. and Harlow Brooks, M. D. Fourth 
edition, thoroughly revised. 1917. S°. 666 pages. W. B. 
Saunders Company, Philadelphia and London. 

The Treatment of Tabetic Ataxia by Means of Systematic Exercise. 

By Dr. H. S. Frenkel. Second revised and enlarged English 

-edition by L. Freyberger, J. P., M. D. (Vienna), M. R. C. P. 

Lond., M. R. C. S. Eng. With 130 illustrations. 1917. 8°. 

209 pages. P. Blakiston's Son & Co., Philadelphia. 

Dr. Lyman Spalding, the Originator of the United States Pharma- 
copoeia. Co-laborer with Dr. Nathan Smith in the Founding 
of the Dartmouth Medical School and its First Chemical Lec- 
turer; President and Professor of Anatomy and Surgery of 
the College of Physicians and Surgeons of the Western Dis- 
trict, at Fairfield, N. Y. By his grandson. Dr. James Alfred 
Spalding. 1916. 380 pages. W. M. Leonard, Boston. 

Operative Surgery of the Nose, Throat, a^id Ear. For Laryngolo- 
gists, Rhinologists, Otologists, and Surgeons. By Hanau W. 
Loeb, A. M., M. D. in collaboration with Joseph C. Beck, M. D., 
George W. Crile, M. D., William H. Haskin, M. D., Robert Levy, 
M. D., Harris P. Mosher, M. D., George L. Richards, M. D.. 
George E. Shambaugh, M. D., and George B. Wood, M. D. In 
two volumes. Volume 11. Four hundred and seventy-six 
illustrations. 1917. 8°. 427 pages. C. V. Mosby Company, 
V St. Louis. 

^Wima, Presenting an Exposition of the Nonpassive Expiration 
Theory. By Orville Harry Brown, A. B., M, D., Ph. D., with 
a foreword by George Dock, Sc. D., M. D. Thirty-six engrav- 
ings. 1917. 8°. 330 pages. C. V. Mosby Company, St. Louis. 

Experimental Pharmacology. By Dennis E. Jackson, Ph. D., M. D. 
With three hundred and ninety original illustrations including 
twenty-four full-page color plates. 1917. 8°. 536 pages. C. V. 
Mosby Company, St. Louis. 

Impotewy, Sterility and Artificial Impregnation. By Frank P. 
Davis, Ph. B., M. D. 1917. 12°. 138 pages. C. V. Mosby Com- 
pany, St. Louis. 

\Tne Climate and Weather of San Diego, California. Prepared 
under the direction of Willis L. Moore, Chief United States 
Weather Bureau. By Ford A. Carpenter, Local Forecaster. 
Illustrated with photographs and charts by the author and 
others. 1913. 16°. 118 pages. Published by the San Diego 
Chamber of Commerce. 



The Adventure of Death. By Robert W. Mackenna. 1917. 12°. 
197 pages. G. P. Putnam's Sons, New York and London. 

Acute Poliomyelitis. By George Draper, M. D., with a foreword 
by Simon Flexner. With 19 illustrations. 1917. 8°. 149 
pages. P. Blakiston's Son & Co., Philadelphia. 

Psychological Medicine. A Manual on Mental Diseases. For 
Practitioners anfi Students. By Maurice Craig. Third edition. 
With 27 plates, some in colour. 1917. 8°. 4S4 pages. 
P. Blakiston's Son & Co., Philadelphia. 

Chemical and Microscopical Diagnosis. By Francis Carter Wood, 
M. D. Third edition. With 194 illustrations in the text and 
10 plates, nine of which are colored. 1917. 8\ 791 pages. 
D. Appleton & Company, New York and London. 

U. S. Department of Commerce, Bureau of the Census. Mortality 
Statistics, 1915. Sixteenth Annual Report. Sam L. Rogers, 
Director. 1917. 707 pages. Government Printing Office, 
Washington. 

Sai7it Thomas's Hospital Reports. New Series. Edited by Dr. J. J. 
Perkins and Mr. C. A. Ballance. Volume XLIII. 191*4. S". 
303 pages. 1916. J. & A. Churchill, London. 

Some Personal Recollections of Dr. Janeway. By James Bayard 
Clark. 1917. 12°. 36 pages. G. P. Putnam's Sons, New York 
and London. 
J - I 

Am,erican Association for Study and Prevention of Infant Mor- 
tality. Transactions of the Seventh Annual Meeting, Mil- 
waukee, October 19-21, 1916. 1917. 8°. 364 pages. Press of 
Franklin Printing Company, Baltimore. 

Notes on Galvanism and Faradism. By E. M. Magill, M. B., B. S. 
Lond., D. P. H., R. C. S. I. (Hons.) With 67 illustrations. 
1916. 12°. 220 pages. Paul B. Hoeber, New York. 

Urology. Diseases of the Urinary Organs, Diseases of the Male 
Genital Organs, the Venereal Diseases. By Edward L. Keyes, 
Jr., M. D.. Ph. D. With 204 illustrations in the text and 18 
plates, four of which are colored. 1917. 8°. 908 pages. 
D. Appleton & Company, New York and London. 

Glaucoma. A Handbook for the General Practitioner. By Robert 
Henry Elliot, M. D., B. S. Lond., Sc. D. Edin., F. R. C. S. Eng., 
etc. Lieut.-Colonel I. M. S. (Retired). 1917. S°. 60 pages. 
Paul B. Hoeber, New York. 



28 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 323 



The British Ouiana Medical Annual. Twenty-first year of issue 
for 1915. Edited by A. J. Craigen, M. B., Ch. B. (Aberdeen) 
and F. G. Rose, B. A., M. B., B.C. (Cantab.) M. R. C. S.. 
L. R. C.P. 1916. 8°. 179 pages. Printed by " The Argosy " 
Company, Limited, Demerara. 

The Medical Association of the Isthmian Canal Zone. Proceedings 
for the half year, .January to June, 1916. Volume IX, part 1. 
1917. 8°. 190 pages. The Health Department, Panama Canal 
Zone. 

Baltimore, Sub-Department of Health. Department of Public. 
Safety. Annual Report to the Mayor and City Council of 
Baltimore for the Fiscal Year Ended December 31, 1915. i<>16. 
8°. 348 pages. Meyer & Thalheimer, Baltimore. 

International Clinics. A Quarterly of Illustrated Clinical LectJVe: 
and Especially Prepared Original Articles. By leading mem- 
bers of the medical profession throughout the world. Edited 
by H. R. M. Landis, M. D. Volume II. Twenty seventh series. 
1917. 8°. 313 pages. J. B. Lippincott Company, Philadelphia 
and London. 

Collected Papers of the Muijo Clinic. Rochester. Minnesota. Edited 
by Mrs. M. H. Mellish, Vol. VIII, 1916. 8°. 1014 pages. 1917. 
W. B. Saunders Company, Philadelphia and London. 

The Treatment of Emergencies. By Hubley R. Owen, M. D. With 
249 illustrations. 1917. 12°. 350 pages. W. B. Saunders Com- 
pany, Philadelphia and London. 

Fi7ich and Baines. A Seventeenth Century Friendship. By Archi- 
bald Malloch, B. A. (Queen's): M. D. (McGill) ; Temporary 
Captain, Canadian Army Medical Corps. 1917. 4°. 89 pages. 
University Press, Cambridge. 

Physical Exercises for Invalids and Convalescents. By Edwar.l 
H. Ochsner. B. S., M. D., F. A. C. S. Illustrated. 1917. \'.'". 
54 pages'. C. V. Mosby Company, St. Louis. 

Roentgen Tcchnie (Diagnostic.) By Norman C. Prince, M. D. 

With 71 original Illustrations. 1917. 8°. 140 pages. C. V. 

Mosby Company, St. Louis. 
E. Merck's Annual Report of Recent Advances in Pharmaceutical 

Chemistry and Therapeutics. Vol. XXVIII. 1914. 8°. 4SS 

pages. Darmstadt, New York City. 
University of Pennsylvania. Henry Phipps Institute for the study. 

Treatment, and Prevention of Tuberculosis. Thirteenth \U 

port. 1917. 4". 459 pages. Published by the Henry Phipps 

Institute, Philadelphia. 

The Carnegie Foundation for the Advancement of Toachi/ta. 
Eleventh Annual Report of the President and of the Treii: ur i 
1916. 4°. 172 pages. New York City. 

Hospital of the Protestant Episcopal Church in Philadelphia. Med- 
ical and Surgical Reports of the Episcopal Hospital. Vol. IV. 
1916. 8°. 326 pages. Press of Wm. J. Dornan, Philadelphia. 

United States, Department of Commerce, Bureau of the Census. 
Abstract of the Census of Manufactures 1914. 1917. 8°. 722 
pages. Government Printing Office, Washington. 

The Elements of the Science of \ulrition. By Graham Lusl<-. 
Ph. D., Sc. D., F. R. S. (Edin.) Third edition reset. 1„17. 
8°. 640 pages. W. B. Saunders Company, Philadelphia and 
London, 

Egypt. Ministry of the Interior, Prisons Department. Interim 
Report of the Prison Diets Committee. 1917. Fol. 63 pages. 
Government Press, Cairo. 



A Monograph on the Epidemic of Poliomyelitu (Infantile Paraly- 
sis) in New York City in 191(1. Based on five Official Reports 
of the Bureaus of the Department of Health. 1917. 40. 391 
pages. Published under the Direction of the Department of 
Health of New Y'ork City. 

Handbook of Gynecology. For Students and Practitioners. By 
Henry Foster Lewis, A. B., M. D., and Alfred de Roule\, b. Sc., 
M. S., M. D. With 177 illustrations. 1917. 8°. 452 pages. 
C. V. Mosby Company, St. Louis. 

Bulletin of Iowa Institutions. (Under the Board of Contn>i). 
Published Quarterly. Vol. XVIII. 1916. 8°. 252 pages. 

The Mastery of Nervousness. Based upon Self Reeducation. By 
Robert S. Carroll, M. D. 1917. 8°. 346 pages. Macmillan 
Company, New York. 

Manual of the Diseases of the Eye. For Students and General 
Practitioners. By Charles H. May, M. D. Ninth edition, 
revised. With 377 original illustrations, Including 22 plates, 
with 71 colored figures. 1917. 8°. 440 pages. William W'ood 
& Co., New York. 

Dream Psychology. By Maurice NicoU, B. A., M. B., B. C. (Camb.) 
Capt. (Temp.) R. A. M. C. 1917. 12°. 194 pages. Henry 
Frowde; Hedder and Stoughton, London, Oxford University 
Press. 

Immune Sera. A Concise Exposition of our Present Knowledge of 
Infection and Immunity. By Charles Frederick Bolduan, 
M. D., and John Koopman, B. S. Fifth edition, thoroughly 
revised. 1917. 12°. 206 pages. John Wiley and Sons, Inc., 
New York; Chapman and Hall, Limited, London. 

Poliomyelitis, in All its Aspects. By John Ruhrah, M. D., and 
Erwin E. Mayer, M. D. Illustrated with US engravings and 
2 plates. 1917. 8°. 297 pages. Lea and Febiger, Philadel- 
phia and New York. 

First Lessons in Spoken French for Doctors and Nurses. By 
Ernest H. W^llklns, Algernon Coleman and Ethel Preston. 
1917. 16°. 137 pages. University of Chicago Press, Chicago, 
Illinois. 

Practical Materia Medica and Prescription Writing. With illustra- 
tions. By Oscar W. Bethea, M. D., Ph. G., F. C. S. Second 
revised edition. 1917. 8°. 562 pages. F. A. Davis Company, 
Philadelphia. 

Bibliography of William Henry Welch. M. D.. LL. D. Prepared 
by Walter C. Burkett, M. D. 1917. 4°. 47 pages. Johns 
Hopkins Press, Baltimore. 

Modern Dietetics. Feeding the Sick in Hospital and Home. With 
Some Studies on Feeding Well People. By Lulu Graves. 1917 
8°. 214 pages. The Modern Hospital Publishing Company, 
St. Louis. Mo. 

The Treatment of Diabetes MeUitus. With Observations upon 
the Disease Based upon 1300 Cases. By F:iiot P. Joslin, 
M. D. (Harv.), M. A. (Yale). Second edition, enlarged and 
thoroughly revised. Illustrated. 1917. 8°. 559 pages. 

Federal Aid for Vocational Education. A Report to the Carnes»e 
Foundation for the Advancement of Teaching. By I. L Kan- 
del. Bulletin Number Ten. 1917. 4°. 127 pages. N«!w York 
City. 

The Roentgen Diagnosis of Diseases of the Alimevtary Canal. By 
Russell D. Carman, M. D., and Albert Miller, M. D. With 504 
original illustrations. 1917. 8°. 558 pages. W. B. Saunderi 
Company, Philadelphia and London. 



The Johnu nopkins Hospital Bulletins are issued monthly. Then are printed hy the LORD R,\I/riHORE PliESS. naltimnre. ®" ''««'.' '*'■'""■ ';%,„ 
a year (forciqn postai/e, .ID rents), nin;; he addressed to the pubUshera, THE JOH\S IIOI'KIXS PRESS, BALTIUORE : tingle copies tcill be leni uv 
mail for filty cents each. Rinale ropira maji also be procured from thr B.\LTIMOliE .VBll'S ro., BaHimore. 



BULLETIN 



OF 



THE JOHNS HOPKINS HOSPITAL 



Entered as Second-Class Matter at the Baltimore, Maryland, Postoffice 



Vol. XXIX— No. 324] 



BALTIMORE, FEBRUARY, 1918 



[Price, 50 Cents 



CONTENTS 



Interstitial Pregnancy. (Illustrated.) 

By B. M. N. Wynne 

Transplantation of tlie Trachea. (Illustrated.) 
By Walter C. Burkkt, M. D. . . . 



r.\QE 

2n 



.•55 



Experiments in the Artificial Production of Amyloid. 

By K. HrROSE 

Abstracts of Papers 

The Use of Free Grafts of Wl.ole-Thickness Skin for the Relief 

of Contractures [.John Staige Davis, JI. D., F. A. C. S. ] ; 

A Rack for Facilitating the Handling of Small Beep Skin 
Grafts [John- Staige Davis, M. D., F. A. C. S.] ;— The Inter- 



relation of the Surviving Heart and Pancreas of tlie Dog 
in Sugar Metabolism— Second Paper [Admont H. Clark] ; 
—A New Method for Making Wasaermann Antigens from 
Normal Heart Tissue [Clarence A. Neymann and Le-Slie 
T. Gager] ;— a New Pathogenic Sporotrichum. Found in a 
Case of Acute Arthritis of the Knee, Following Injury 
[S. B. Wolbach, M. D., W. R. Sisson, M. D., and F. C. 
Meiek, Ph.D.]. 

Titles of Papers Appearing During the Year, Elsewhere than 
in the Bulletin, by Present and Former Members of the 
Hospital and Medical School Staff 47 

Books Received . ' 54 



INTERSTITIAL PKEGNANCY 



By H. iJ. N. Wynne, 



Assistant Residrk 
(From the Gynecological Department 

Ectopic pregnancy in tlie interstitial portion of the Fallo- 
pian tube is of especial interest on account of its infrequoiicy 
and from the standpoint of diagnosis. 

•Several authors have given Pierre Dionis credit for being 
tlio first to describe a case of interstitial pregnancy, published 
in 1718 in his Traite General des Accouchement^. We find, 
iK^ver, that Dionis cites cases of tubal pregnancy he had seen" ' 
with a drawing of one specimen, in which the foetus lay in the 
ampulla oi the right tube, and discusses Mauriceau's famous 
case in which he says the fojtus was formed in the extremitv 
of the tube which terminates in the uterus. (" Tous c'eux qui 
ont examine ce fait, sont convenus que eet enfant avait ete 
etZ - '-"' 'r*''^""^ de la rompe qui aboutit a la matrice, 

tZl .r '^'"' ^'°P""°" d-^^ °«'^f«-") According to 

Uionis, Mauriceau claimed that this fcBtus had been formed 
n tl e uteru.. and said that he would never accept any case of 

it, !r'""'l """" *'"-^' -"t^^d-.ted his theory and doc- 
irme of generation. 

vassal and others, was that of a woman of 32 years who had 
..ven birth to 11 full-term babies, and during thTtMrd mend' 



t Gynecologist 
of The Johns Hopkins Hospital) 

of her twelfth pregnancy died after having had violent abdomi- 
nal pain, fainting attacks and convulsions for three days. This 
case was the basis of a long and heated discussion carried on 
between Mauriceau and Graaf, Dionis and other less celebrated 
men, who believed it, with Vassal, to be a tubal pregnancy. As 
we have seen, Dionis held that it was of the interstitial variety. 
The drawing published by Mauriceau illustrates very well a 
pregnancy in a rudimentary horn, although the author de- 
scribed it as a hernia of the uterine cornu. Mauriceau takes 
pains to explain that his drawing was the only correct one, as 
Vassal's was constructed from memory over a month after the 
autopsy and had been changed by others, who had copied it, 
to agree with their ideas. 

Schmidt (1801) is generally credited with having reported 
the first authentic case. A treatise on this subject, with a dis- 
cussion of four cases, was published in 1825 by Mayer. Brechet 
reported cases in 1826 — Hedrick's, Bellemain's, Schmitt's and 
Dance's (Simon). 

The first case reported by an American was by T{. H. Fitz, 
of Boston, in 1875. The specimen, having been obtained at 
autopsj', was presented to him by A. T. Davison, who also 



30 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 324 



furnished the clinical history. Fitz published drawings and 
a careful description of the specimen after reviewing the litera- 
ture, from which he accepted 18 cases. In 1885 Simon analysed 
the 40 cases reported to that time, nine of which he considered 
undoubtedly true interstitial, nine as doubtful and the remain- 
ing 24 as ectopic pregnancies of other types. Werth, in 1904, 
considered 40 cases above criticism, but Weinbrenner in the 
same year believed that five of these were not to be allowed. 
Since these reviews, additional cases have been collected from 
the literature or reported by the following : Finsterer, 17 cases 
in 1908; Lequeux, 12 cases in 1911; Schenk, 19 cases in 1912, 
and Farrar, 10 cases in 1914. Of these reports, there are several 
overlapping, as Schenk gives seven previously mentioned by 
Lequeux and Farrar, one of which was reported by Schenk. We 
have not attempted to review the individual cases cited by 
these several authors. If all were to be allowed, the total to 1914 
is 85 cases. The subject hs been discussed very thoroughly, 
and references to a fairly large literature have been given by 
the authors mentioned above. I 

OCCURRENCE 

The percentage of interstitial pregnancies in all types of 
ectopic gestation is usually stated as 3 per cent. This is based j 
on the work of von Rosenthal, who collected from the litera- 
ture 1324 cases of all types before 1896 and 40 cases of inter- 
stitial pregnancy reported during the same time. According i 
to the more recent works of Werth and Weinbrenner, there were 
considerably less than 40 cases of true interstitial pregnancy 
at that time. 

We believe that a more accurate method of determining the 
percentage is to total several series from the larger clinics, in 
which careful differential diagnoses have been made. These 
figures are as follows: 

Casea 

Baculescu reported one interstitial in a series of 58 

Finsterer reported one interstitial in a series of 133 

Kastaneff (Wasten's clinic) reported eight interstitial in a 

series of 335 

Krivsky reported two interstitial in a series of 223 

Lahostky reported two Interstitial in a series of 150 

Mandl and Schmidt reported no interstitial in a series of. .. . 77 

Martin reported one interstitial in a series of 77 

Talt reported one interstitial in a series of 100 

Werth reported no interstitial in a series of 120 

In this clinic there have been 304 cases of ectopic pregnancy 
operated on, only two of which can be classed as interstitial. 
In a total of 1547 cases of ectopic pregnancy, there are 18 cases 
of interstitial pregnancy (1.1(5 per cent). 

CLASSIFICATION 

The classification and dilTorontiation of interstitial preg- 
nancy have been thoroughly discussed by Weinbrenner, Kohl- 
mann and Lequeux. Tlio implantation of the ovum must be 
in the interstitial portion of a tube, including diverticula from 
the tube, extending into uterine muscle. But in view of the 
fact that the development of the embryo may change anatomi- 
cal relations to some extent, various classifications have been 



proposed ; that of Klebs will cover most of the conditions found 
at operation and is as follows : 

(1) Graviditas utcro-interstitialis, 

(2) Graviditas tubo-interstitialis, 

(3) Graviditas interstitialis propria. 

DIAGNOSIS 

The distinguishing details of the differential diagnosis be- 
tween this type and pregnancy occurring in other portions of 
the tube or in a rudimentary horn may be found tabulated in 
Farrar's paper. 

Virchow noted that the round ligament is always outside 
of the gestation sac. The insertion of the round ligament is 
usually lateral and inferior or anterior and inferior to the 
gestation sac. Glaesmer says that in his case the round liga- 
ment was medial to the sac and discusses this phase of the 
diagnosis at length. Lequeux says that the variations in the 
insertion of the round ligament are due to the variety of im- 
plantation and to the evolution of the ovum. The relation of 
the proximal end of the tube to the gestation sac is subject 
to variation also. The tube is usually inferior, but can be more 
or less lateral according to the development of the ovum. Von 
Rosenthal believed that the tube was always inserted into the 
inferior border of the gestation sac. 

According to several more recent papers Ruge's sign is not 
always present. This sign, as stated by Simon, ia that the 
distance between the insertions of the tube and round ligament 
is increased and the adnexa of the affected side are higher than 
on the other side, owing to the increase in size of the pregnant 
horn and some rotation of the uterus following this asjTn- 
metrical development. A positive diagnosis of interstitial 
pregnancy before operation is, we believe, very unlikely. Kelly 
described a type of apical pregnancy which may be mistaken 
for the interstitial variety, in which there is often severe pain ; 
and on examination the softening and enlargement of the 
uterus is confined to one apex, even as late as the fifth month, 
but these terminate nonnally. He also states that they may 
be interstitial pregnancies with the ovum lodged very '" 
uterine cavity and become intrauterine secondariN-. ;.l rwu-.. 
he does not interpret them as such. 

There are also early isthmial pregnancies developinj vc./ 
close to the uterine cornu, difficult to diagnose at operation. 
In this clinic the diagnosis at operation in seven cases has been 
cornual pregnancy, but on careful histological stady only two 
have proven to be interstitial in origin. 

Pregnancy in one horn of a bicoruuate ucerus may in ccrtam 
cases present a serious difficulty in making the differentia' 
diagnosis, as also can a small myoma in one cornu or a uni- 
lateral cornual abscess, especially when associated with the 
retained membranes of an early abortion. 

Sturmdorf made a diagnosis of ectopic pregnancy on the 
right side, but at operation the right-sided ^nass proved to be 
a tubo-ovarian abscess, and in the left cornu, which was thought 
to be normal, there was an early interstitial pregnancy. 

Robin's case was diagnosed ectopic pregnancy or acute appen- 
dicitis, and an exploratory McBurney incision made to deter- 



February, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



31 



mine the exact condition. In the case reported by Schenk, 
the pre-operative diagnosis was correct and the pre-operative 
diagnosis in Schumann's case made by Hirst proved to be 

right. 

Levers considers persistent amenorrhcea a very important 
si on in the differential diagnosis. Our investigation of 36 
cases showed that amenorrhcea was persistent in 12, tlie periods 
were quite regular in two and irregiilar bleeding occurred in 
22 cases, although it was very slight in five of these. 

Siefart claims that no interstitial pregnancies are seen after 
the sixth month; but Ferguson reports a case which he con- 
sidered primarily interstitial and secondarily abdominal, 
operated on by him at term, but his report is too incomplete 
to establish the diagnosis above criticism. Cases have been 
reported in which an 8-month foetus was found by Kupferberg 
and a 7-month foetus by Glaesmer. Pegaitaz performed a 
supravaginal hysterectomy for myomata on a patient who had 
shortly before given birth spontaneously to a 6^-month foetus. 
On examining the uterus, he found the placenta in the inter- 
stitial portion of the tube. 

Beckmann and Siefart believe that perforations always occur 
on the posterior convex surface of the gestation sac. In 20 
eases in which we have found the site of rupture mentioned, 
it is described as on the posterior surface in eight, on the pos- 
terior superior surface in five, on the posterior lateral surface 
in one, on the superior surface in three, on the superior anterior 
surface in two, and on the anterior surface in one. This last- 
mentioned case was exhibited in 1903 by Seitz. 

Rupture generally occurs during the first half of pregnancy. 
There is at present a considerable number of patients in the 
literature who were operated on before rupture had occurred. 
The statistics are as follows : 



Ruptured 



Mouth 
1... 
1-2. 
2... 

2-3. 
3... 
3-4. 
4... 
4-5. 



5-6. 
6... 

7... 



Werth 
1 
3 
4 
6 
4 
2 
4 
4 
3 
1 



Operated 
on Uii- 
Ruptured ruptured 
2 2 



These statistics show that the most usual time for rupture 
■-S during the second and third months. The statistics of Baart 
de la Faille, Henning and Parry (quoted from Eckert) show 
that rupture occurs most frequently between the third and fifth 
months. The tables given above, however, include cases that 
have been more strictly criticised than those of the authors 
mentioned, as well as the recent cases. 

There have been two other cases reported as unruptured, but 
the age of the foetus was not stated. The total number of cases 
up to 1917 is about 91, and 21 of these were unruptured 
(about 23 per cent). 



The ages of the patients in 38 cases are as follows : 



Years 
21. 
24. 
25. 
26. 
27. 
28. 
29. 
30. 



No. of patients 

1 

2 

4 

1 

3 

6 

3 

2 



No. of patients 
2 



The decade between 25 and 35 years shows the greatest 
nimiber of cases. 

In a series of 42 cases the numbers of pregnancies prior to 
the interstitial pregnancy are as follows: 

No. of pregnancies No. of cases Miscarriaffes 

5 

1 13 1 (induced). 

2 11 2 pts. had 1 each, and 1 pt. 2 (induced). 

3 5 1 patient had 1. 

4 4 1 patient had 2. 

5 2 

9 1 7 miscarriages. 

16 1 2 miscarriages. 

The time elapsing after the last pregnancy before the inter- 
stitial pregnancy in 19 cases was as follows: 



Time No. of cases 

2 months 1 

7 months 1 

11 montlis 1 

1 year 2 

16 months 1 

2 years 1 

2y2 years 1 

3 years 4 



4 years 1 

5 years 1 

6 years 1 

7 years 1 

11 years 1 

13 years 1 

14 years 1 



CAUSE 

Conditions that bring about the abnormal embedding of the 
ovum in other portions of the tube are doubtless responsible 
for the occurrence in this portion as well. Dionis (1718) 
argued that the interstitial part of the tube should be the 
seat of tubal pregnancy more often than any other part of 
the tube ; owing to its smaller calibre, however, there are fewer 
folds of the mucosa in this section and the lumen is less en- 
croached upon by inflannuatory changes than at any other part 
of the tube. Frankl considers the presence of diverticula of 
the utmost importance as a cause of interstitial pregnancy. 

We shall not repeat the numerous theories advanced to 
explain the cause of tubal pregnancy, as they have been dis- 
cussed in many of the papers on this subject. 

Scott believes previous curettage responsible for some cases, 
but this theory is difficult to uphold, as, in curettage of the 
uterine cavity, the apices are practically never injured; tliis 
can be demonstrated by opening a uterus removed immediately 
after a careful curettage. 

Nache attempted to sterilize a woman by making a wedge 
excision of the tubes from the uterus, but four months later 
was obliged to perform a laparotomy for an interstitial preg- 
nancy. 



33 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 334 



The right tube and ovary were absent and the right uteriue 
cornu was the seat of an interstitial pregnancy in a case 
operated on by Andrews. 

TREATMENT 

The first operation for insterstitial pregnancy was performed 
on October 15, 1893, by Traub, who did a supravaginal hyster- 
ectomy, and on October 23, 1893, Lawson Tait operated on a 
case by incising the sac, evacuating the contents and draining. 
Since that time the treatment of choice has been operative, 
as soon as a diagnosis has been made which indicated opera- 
tive interference, and in the great majority of cases this has 
been done after rupture of the sac. Immediate operation is 
most important in this type of ectopic pregnancy on account 
of the enormous hemorrhage that ahnost always follows rup- 
ture and the small chance that the bleeding will cease before 
the patient is moribund. 

A great variety of operations have been done for this con- 
dition. In 66 cases the following operations have been per- 
formed : 

VAGINAL 

Times 

Panhysterectomy 1 

Wedge excision of cornu 1 

ABDOMINAL 

Times 

Panliysterectomy 2 

Panliysterectomy witli double salpingo-oopliorectomy . . 1 

Supravaginal hysterectomy 17 

Supravaginal hysterectomy with drainage 1 

Resection of uterine cornu 8 

Resection of uterine cornu with salpingectomy 1 

Resection of uterine cornu with salpingo-oophorectomy. 1 
Resection of uterine cornu and digital cleaning of 

uterine cavity from above 1 

Resection of uterine cornu and curettage of uterine 

cavity from above 1 

Excision of uterine cornu with salpingo-oophorectomy. 2 

Excision of gestation sac 9 

Excision of gestation sac with salpingectomy 1 

Excision of gestation sac with salpingo-oophorectomy. 4 

Wedge excision of cornu 8 

Wedge excision of cornu with salpingo-oophorectomy. 2 
Incision of gestation sac, evacuation of contents and 

drainage 1 

Cleaning out sac and suture of wound 2 

Cleaning out sac and suture of wound, with drainage 

through the uterus 1 

Dilatation and curettage followed by laparotomy, with 

incision into sac, evacuation of contents, uterine 

cavity opened, suture of wound, myomectomy 1 

Dilatation of cervix and removal of intrauterine ovum 

with forceps, followed by laparotomy with a wedge 

excision of the cornu, uterine cavity not opened .... 1 

The abdominal route has been used in all but two cases and 
undoubtedly is the best. The type of operation must be selected 
to fit the emergency, as in the more advanced cases hyster- 
ectomy is usually preferred and in the earlier cases excision 
of the cornu with suture usually can be done more quickly. 
Speed is almost always to be considered, as the majority of 
these patients are in bad condition. 



Schurmann's patient was treated expectantly for three 

weeks, when, on account of continued pain, the uterus was 

explored digitally, the gestation sac broken into, a 4-month 

foetus witli the placenta was removed and the uterihe cavitv 

curetted. 

Farrar, following Kelly's suggestion, after having opened 

tlie abdomen and finding no rupture, curetted the gestation 

sac from below, giiarding against puncture with one hand in 

the abdomen. 

The interval between the onset of acute symptoms and opera- 
tion has been as follows : 

Ward's case 4 hours. 

Polak's case 4-5 hours. 

Glaesmer's case 6% hours. 

Siefart's case 7 hours. 

Kohlmann's case 11 hours. 

J. H. H. Gyn. No. 20777 12 hours. 

Nacke's case 24 hours. 

Lequeux's case 24 hours. 

Punke's (Kuhlmann) case 36 hours. 

Andrew's case 3 days. 

Weinbrenner's case (1) 14 days. 

V. Hoist's case 14 days. 

Muret's case had ruptured some time before and closed off by intes- 
tinal and omental adhesions; the foetus was four and one- 
half months old. 

CuUingworth's case ruptured at the third month; the operation 
was done five months after conception; the foatue had been 
dead some time before the operation. 

Treub's case ruptured at the third month, secondary abdominal 
pregnancy developed, foetus measuring 41 cm. when removed. 

Farrar's case unruptured; severe vaginal haemorrhage a few hours 
before operation. 

J. H. H. Gyn. No. 15342, unruptured; haemorrhage through tube 
into abdomen; onset 16 days before operation. 

PROGNOSIS 

All authors agree that the prognosis in this type of ectopic 
pregnancy is extremely grave. Werth in a series of 31 
operated cases found four deaths; Finsterer, two deaths in 
17 cases; Schenk, four deaths in 19 cases (no operation in two 
cases). Lequeux reports two deaths in five cases (no opera- 
tion in one case) and Farrar 10 cases with one death, while 
in the five undoubted cases since the latter's paper there were 
no deaths. (Two of Schenk's cases included in Lequeux's 
report (one death) and one of Farrar's cases reported by 
Schenk.) In 82 operative cases there were 10 deaths or a 
11.9 per cent mortality with operation. 

Prior to 1893, all the cases in the literature lunl been found 
at autopsy. Of the nine undoubted cases analysed by Simon 
in 1885, the time from the onset of symptoms due to ruptwe 
until deatli was less than 12 hours in two cases, less tJ«ui 24 
hour in four cases, 27 hours in one case and 15 days in one 
case. 
Wagner's patient (Case 111) died 17 hours after an acute onset, 

while being prepared for operation. A 6-week foetus was 

found at autopsy. 
Kupferberg's patient died 48 hours after an acute onset, while 

being prepared for operation. 

was found. 



At autopsy an 8-month foetus 



'EBKUAIiY, 1!)18| 



JOHNS HOPKINS HOSPITAL BULLETIN 



33 



Eckert's patient died 15y2 liours after an acute onset. A 3-montli 
foetus was found at autopsy. 

Bar and Bufnoir's patient died Ave days after an acute onset. At 
autopsy a foetus weighing 1025 grams was found. It liad evi- 
dently been alive until tlie time of rupture. 

'I'lu' raii-r of death ( |)ost-()perative ) in nine ca.ses was stated 
I- follows : 

llonnaire and Brae's patient was about six weeks pregnant. The 
cervix was dilated, the uterine cavity curetted and an intra- 
uterine injection of iodine given, followed by death 4.5 minutes 
later. At autopsy no cause for death found. 

Funke's (Kiihlmann) patient ruptured at the third month; the 
first acute symptoms had appeared 35 hours before operation. 
She was in shock when operated upon, and died one and one- 
quarter hours later. Supravaginal hysterectomy was per- 
formed. 

Glaesmer's patient had ruptured probably six and one-half hours 
before operation. She was in shock when operated upon, and 
died three hours later. A 7-month dead fffitus was removed at 
operation by panhysterectomy with bilateral salpingo-oopho- 
rectomy. 

Koblanck's (Opitz) patient was in shock when operated upon, and 
died a few hours later. A 1 to 2-month pregnancy was re- 
moved by a wedge excision of the cornu with suture. 

Kynock's patient was in poor condition when operated upon, 
although the sac had not ruptured. A 4-month pregnancy was 
removed by supravaginal hysterectomy. The patient died 
three days later from hiemorrhage from the cervical stump. 

Olhausen's (Opitz) patient was in shock when operated upon, and 
died a few hours later. A 1 to 2-month pregnancy was re- 
moved by a wedge excision of the cornu with suture. 

Raschkes' patient had ruptured when three and one-half months 
pregnant. A resection of the uterine cornu was done, and the 
patient died eight days later with symptoms of a general 
peritonitis. 

Siefart's patient had ruptured seven hours before operation. A 
2-month pregnancy was removed by resection of the uterine 
cornu, and death occurred 12 hours later from shock. 

Weinbrenner's patient (Case II) underwent a resection of the 
uterine cornu for a 4-month infected pregnancy; the fcetus was 
macerated. Deatli occurred three days later from general 
peritonitis. 

REPORT OF CASES FROM THE LITERATURE 
Since tlif publii-ation ol' Farrar's paper, there liave been 
IT oases published, of which only three have been reported 
hv full, with ■ iiathological and histolo.tjical descriptions. A 
thorough microscopic study is neces.sary in many cases to prove 
the diagnosis beyond criticism, although only a small number 
have been studied carefully in this way. Eckert states that 
uj) to 1904 only three cases had been submitted to microscopic 
studies, Ulessko-Stroganowa's, Leopold's and Easchkes'. 

The undoubted cases are Mangiagalli's (fully reported bv 
Colombino in 1911) and Popoflf's two cases (in 1914). 

Probable cases have been reported by 
Czyzewicz, 2 cases, 1914. (No illustrations; no patliological report. ) 
Gibson, 1 case, 1914. (No illustrations; incomplete pathological 

report. ) 
Heyman, 1 case, 1915. 

Kastaneff, 4 cases, 1914. (No illustrations: no microscopic re- 
port.) 
Kohlman, 1 case, 19 Ki. (No pathological report.) 
Leonormant & Hartmann, 1914. 2 cases in a series of 37 tubal preg- 
nancies (descriptions incomplete). 



Oastler, 2 cases, 1915. (No illustrations; no pathological report.) 
Viannay, 1 case, 1913. (No illustrations: no microscopic report.) 
Vineberg, 2 cases, 1915. (No illustrations; no pathological report.) 

One case was operated on by himself and one case he saw at 

autopsy. 

REPORT OP CASE 

Gyn. No. 20777. — The patient was a white woman, 24 years old, 
married Ave years, who had had a normal labor and puerperium 
three years before and had had no miscarriages. Six years before 
admission she had had an attack of abdominal pain diagnosed as 
appendicitis, but had not been operated upon tor it. The past his- 
tory was otherwise negative. 

Her last regular period began August 1, 1914; since that time 
amenorrhcea had persisted. She considered herself pregnant. 

At 1 p. m., November 29, 1914, she fell down stairs, and at 1.30 
p. m., while attending to her household duties, she was seized with 
violent general abdominal pain and lay down on the floor, where 
she remained until carried to bed. The pain continued very severe 
all the afternoon and at 5 p. m. she vomited. She noticed that her 
abdomen was becoming larger and was very tender. A physician 
was called to see her and brought her to the hospital with a diag- 
nosis of an acute ruptured appendix. At 11.55 p. m., November 29, 
1914, she was admitted to the hospital. 

Physical Examination. — The patient is a well-nourished and 
well-developed woman in much pain. The skin and mucous mem- 
branes are extremely pale; the skin is cold and covered with sv^eat; 
the pulse is 160, small and weak; the temperature (rectal) 99°F. 
The abdomen is distended, tense, very tender, and movable dullness 
is demonstrable. 

Diagnosis. — Ruptured extra-uterine pregnancy. 
The patient was taken to the operating-room at once and pre- 
pared for operation. Under ether ana-sthesia the pelvic examina- 
tion revealed a uterus twice the normal size. A small nodule was' 
felt in the right uterine cornu and a soft mass in the right fornix 
(suggesting clot). W. B. C. 20,000. Hb. 70 per cent (Sahli). 

Operation. — At 1.30 a. m., November 30, 1914. by Dr. J. C. Neel, 
Resident Gynecologist. 

When the abdomen was opened through a midline incision below 
the umbilicus a large amount of fluid blood and fresh clots escaped 
(estimated at two liters). A nodule measuring 2.5 cm. in diameter 
was seen in the right uterine cornu, on the posterior surface of 
which there was a perforation 1 cm. in diameter, through- which 
placental tissue bulged. There was no active bleeding. The at- 
tachment of the round ligament was anterior to the gestation sac. 
A few flne adhesions were found about the right adnexa; the left 
tube and ovary were normal. 

The uterine cornu and a small portion of the right tube were 
rapidly resected, the uterine cavity was opened and cleaned out 
with the linger. The wound was then sutured with catgut and the 
raw area covered by suturing over it a fold of the round ligament. 
Fluid blood and clots were quickly cleaned out of the abdominal 
cavity and the abdomen was closed in layers. 

A subcutaneous infusion of normal salt solution was started 
during the operation and continued in the ward, 1500 cc. In all 
being given. 

The patient made a rapid recovery and was discharged from the 
hospital in good condition, December 13, 1914. 

The haemoglobin curve in this case is interesting. 
On admission 11/30/14, 1 a. ra.. .KB = 70? (Sahli) W. B. C. 20,000. 
11/30/14, 3 p. m.. . " = 50* (Sahli) W. B. C. 12,000. 

12/1/14 " =34'/ (Sahli) 

12/2/14 " = 30^ ( Sahli ) 

12/3/14 " = 40* ( Sahli ) 

12/6/14 " = 45:? ( Sahli ) 

12/10/14 " =55? (Sahli) 

12/13/14 " =59j( (Sahli) 



34 



JOHNS HOPKINS HOSPITAL BULLETIN 



[Xo. :3'>4 



Somewhat similar lisemaglobin curves have been found in a series 
of cases of acute haemorrhage followed by Dr. Dunn and myself 
during the past two years. 

Specimen from Gyn. Xo. 20777. Anatomical No. llSS.—The 
specimen consists of the right uterine cornu and 1.5 cm. of the 
tube. It measures 3.5 X 2.5 X 2.5 cm. The posterior superior wall 
bulges out, and in the most prominent area there is a perforation 
measuring 1 cm. in diameter, through which a mass of chorionic 
villi protrudes. At the proximal end of the specimen there is a 
small area of endometrium, measuring S mm. in thickness. The 
portion of tube accompanying the specimen measures 5 mm. in 
diameter. 

A longitudinal section of the specimen shows a gestation sac 
measuring 2 cm. in diameter, which is filled with blood-clot, 
and chorionic villi, surrounded by uterine muscle which, between 
the gestation sac and endometrium, measures 2 cm. 

Microscopic Study. — There is a marked decidual reaction of the 
endometrium, areas of markedly hypertrophied uterine glands 
(spongy layer) and other areas of slightly hypertrophied glands. 
There is some infiltration with polymorphonuclear and mono- 
nuclear leucocytes. The vessels are gorged with blood. 

The cells of the myometrium are hypertrophied. The gestation 
sac is surrounded by uterine muscle which, over the posterior wall, 
is thinned out to 2 mm. in thickness (the perforation was above 
this section). The muscular wall lies between the gestation sac 
and the proximal section of the isthmus of the tube. 

The peritoneal surface is covered with a single layer of cells, 
varying from the cuboidal to flat types, with light-staining cyto- 
plasm and uniformly dark-staining nuclei lying about the center 
of the cells. 

Two vessels in the muscular layer show marked hypertrophy 
of the endothelium. Syncytial cells have invaded the muscle and 
opened up blood spaces. A thin layer of decidual cells can be 
seen in some areas, but there is no continuous decidual layer. No 
tubal mucosa can be found. Masses of chorionic villi in blood-clot 
are present; some villi are cedematous and are covered by the 
syncytial layer only, while others have well preserved Langhans 
and syncytial layers. No amnion was found. The fcetus was not 
found. 

A cross section of the tube between the uterine cavity and the 
gestation sac shows strands of two layers of epithelial cells in 
apposition for the most part, but in one or two areas these two 
layers are separated by small spaces showing that the lumen has 
been compressed. The cilia can be seen on these cells. The tissue 
between these strands of epithelium is composed of a very vascular 
connective tissue infiltrated with small round cells. At one edge 
of the tube there is a small, irregularly shaped lumen. At the 
edge of the circular muscle layer there are several spaces ap- 
parently due to splitting of the muscle. 

The istlimus of the tube shows no evidence of inflammatory re- 
action. The folds of the mucosa are normal; cilia are present, 
there is no liypertrophy of the muscle and no decidual reaction 
can be found. 

It seems probable that in this case the ovum was arrested in thn 
interstitial portion of the tube, owing to this inflammatory condi- 
tion just described. 

Gv.v. No. 15:542. — The patient was a negress 35 years old, married 
IS years, who had one full-term child 11 years before and had had 
no miscarriages. The labor and puerperium were normal. There 
was no history suggesting pelvic inflammatory disease. Menstrua- 
tion had been normal. The last period had begun, November 16, 
1908, and had continued the usual tour days. No periods had been 
missed and there was no history of intermenstrual bleeding. 

Present Illness. — At 7 p. m., November 23, 1908, she was seized 
with a severe cutting pain in the R. L. Q. of the abdomen, which 
lasted until 4 a. m., November 24, 1908. A similar attack had 
occurred on December 1, 1908, accompanied by nausea and vomit- 
ing, and again, on December 3, 1908, she had had an attack localized 



in the umbilical region, accompanied by nausea and vomiting, and 
the patient fainted while walking to her bed. For the five days 
before admission she had had burning with frequency and diih- 
culty on voiding. For two weeks there had been a foul, irritating 
vaginal discharge, not bloody. She had felt giddy frequently and 
had been confined to bed most of the time after onset. 

Phijsical Ea-aminatioti. — On admission. December 6, 1908. Tem- 
perature 99°. Pulse 96, good quality. The mucous membranes are 
pale. The breasts contain colostrum. There is a small umbilical 
hernia and a right inguinal ♦hernia: otherwise the abdomen is 
normal. 

Pelvic Ed'aininati07i. — There is no evidence of infection of Bar- 
tholin's glands or of the urethra. The cervix is enlarged but other- 
wise normal. The fundus is in antepositlon and movable. The 
adnexa are adherent, thickened and tender. There is a small 
nodule in the right uterine cornu. 

December 9, 1908. Examination under ether ansesthesia dis- 
closes no abdominal masses. A slight chocolate-colored discharge 
is present. The cervix is enlarged but firm. The fundus is about 
normal in size; it is adherent in mid-position and there is a soft 
mass in the right uterine cornu. The ovaries are adherent. 

Diagnosis. — Chronic pelvic inflammatory disease. (Elxtrauterine 
pregnancy was not suspected.) 

December 9, 1908. Operation by Dr. Casler. Resident Gynecolo- 
gist. 

When the abdomen was opened through a midline incision below 
the umbilicus, a large quantity of old, dark, clotted blood was seeii. 
At the right uterine cornu there was a soft cystic tumor, the size 
of a small lemon. The right tube was practically normal except 
for a slight oozing from the fimbriated extremity. The left adnoxa 
were adherent. The insertion of the round ligament was anterior 
and lateral to the tumor. The right tube and uterine cornu were 
resected, the wound was sutured with catgut and the raw area 
covered by suturing a fold of the round ligament over it. -A 
cigarette drain was placed through the posterior vaginal vault. 
During the operation the specimen was ruptured and a very small 
deformed fo?tus escaped. 

The abdomen -was irrigated with normal salt solution and 
closed In layers. The patient made a satisfactory recovery and 
was discharged, December 23, 1908. 

Gyx. Path. No. 14277. — The specimen consists of a Fallopian 
tube and cornu of the uterus. The tube measures 6 cm. in length, 
with an average diameter of 9 mm.; it is somewhat nodular, the 
fimbriated extremity is open. There are no adhesions over the 
surface. The cornu measures 4 X 3 X 3 cm. ; there is an opening 
on the upper surface 1 X 1.5 cm., with a cavity 2 X 1.5 cm. which 
is lined with a smooth greyish tissue. The wall of this cavity is 
8 mm. thick and is evidently a cavity in which pregnancy has 
existed. The opening between the tube and cornu is patent. (The 
specimen has been preserved in 50 per cent alcohol. The photo- 
graph was made in 1915 and shows where the original blocks for 
microscopic study were cut A number of other blocks have been 
cut since.) 

Microscopic Study of Specimen (Path. Xo. J'i277).—The inner 
lining of the cavity consists of the amnion, which is well pre- 
served. Immediately below the amnion lies the chorion; in mo»' 
instances the villi show more or less degeneration, but in some 
Langhans and the syncytial layers stain clearly. Between the villi 
there are fibrin and collections of leucocytes (largeUv polymor- 
phonuclear cells). Syncytial cells can be seen invading the mus- 
cular wall and there are several areas of decidual cells, although 
there is no uniform layer of decidua. 

In the region of the gestation sac there is no evidence of any 
tubal mucosa or of any uterine glands. 

The gestation sac is completely surrounded by muscular wall, 
except over the posterior superior surface, whore there is an open- 
ing in the sac. About 1 cm. lateral to this opening, a section shows 
the uterine wall completely destroyed and villi extending through 



February, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



35 



the gap, which measures 2 mm. in width. In the muscular layer 
of the posterior wall there are two cavities, lined with a single 
layer of epithelium, varying from a low cuboidal to the rather high 
columnar type; the cells are large, having a dimly staining or 
clear cytoplasm and large, oval nuclei containing from one to four 
deep staining nucleoli; no cilia can be seen on these cells. There 
is no special arrangement of muscle around these spaces. The 
tube proximal to the gestation sac cannot be found. There is no 
endometrium. 

A section through the uterine cornu distal from the gestation 
sac shows the interstitial portion of the tube and three other 
cavities, one of which is similar to those described in the posterior 
wall; the other two are larger and are lined with a single layer of 
poorly staining epithelium, varying from almost flat to the low 
columnar type. These cavities are filled with blood pigment and 
debris of cells. The interstitial portion of the tube shows some 
hypertrophy of the epithelium. There is no definite evidence of 
inflammatory reaction. 

In the isthmus of the tube, vessels are gorged with polymorpho- 
nuclear leucocytes and there is some polymorphonuclear Infiltra- 
tion outside the longitudinal muscle layer. The folds of the tube 
are not thickened and are not adherent; the cilia of the epithelial 
cells can be seen; the lumen is clear. 

In the ampulla of the tube there is a small amount of free blood. 
Many vessels are filled with polymorphonuclear leucocytes, but 
there is no leucocytic infiltration of the tube walls and no other 
evidence of inflammatory reaction. 

No decidual reaction outside the region of the gestation sac can 
be found. 

I wi.sli to thank I)r. Howard A. Kelly fur permission to 
publish these cases and for the interest he has taken in the 
pajjer. Dr. George L. Streetor, Dr. T. S. CuUen, Dr. Daniel 
Davis and Dr. W. R. Hohnes have kindly assisted me in many 
ways. The mtmerous and excellent sections for microscopic 
study were prepared by ]\Ir. Miller and Mr. Robinson. 

LITERATURE 

Andrews: Proc. Royal Society Med., Section Obs. & Gyn., 1912. 
VI, 52. 

Baculescu; Rev. de chir., 1912, No. VI, p. 94G. 

Breschet: Memoire sur une nouvelle espece de grossesse ex- 
trauterine. Rappert general d'anat. et de physiol., Paris, 1826. 

Colombino: Ann. di Ostet., Milano, 1914, p. 374. 

Czyzewicz: Przegl. chir. i ginek., Warszawa, 1914, X, 268. 

Dionis: Traite general des accouchements, Paris, 1718, pp. 79-80. 
A General Treatise of Midwifery (translation), London, 1719, pp. 
81-82. 

Isckert: Inaug-Diss., Miinchen, 1911. 

Farrar; The Post-Graduate, 1914, XXIX, p. 168. 

Pergussou: Jour. S. Carolina Med. Ass., 1913, IX, 271. 

Finsterer: Ztschr. f. Heilkunde, 1908, (Supplement), XXVIII. 

Fitz: Amer. Jour. Med. Sci., 1875, Vol. LXIX, p. 95. 



Frankl; Kurzegefasstes Handbuch der Gesammten Prauenheil- 
kunde, Liepmann, Band II, S. 172. 

Gibson: Tr. Royal Academy Med. Ireland, Dublin, 1914, XXXII, 
292. 

Glaesmer: Arch. f. Gynak., XCIII, p. 125. 

Heyman: Hygiea, Stockholm, 1915, LXXVII, 529. 

Johnson: Boston Med. and Surg. Jour., CLXI, p. 822. 

Kastaneff : J. Akush. i jensk boliez, St. Petersb., 1914, XXIX, 181. 

Kelly: Operative Gynecology, Vol. II, pp. 508, 510 and 534. 

Kohlmann, New Orleans Medical and Surgical Journal. 1912- 
1913, LXV, 5SS. 

Kohlmann: New Orleans Medical and Surgical Journal. 1916- 
1917, LXIX, 210. 

Kiihlmann: Inaug.-Dissert., Strassburg, 1900. 

Lenormant & Hartmann: Rev. gynec. et chir. abdominale, 1914- 
1915, XXIII, No. 4, p. 273. 

Lequeux: Obstetrique, Mai, 1911, t. IV, p. 493. 

Lewers: Lancet, London, 1911, p. 9. 

Mangiagalli: Atti. d Soc. lomb. di sc. med. e biol., Milano, 1912- 
1913, II, 293-296. 

Markoe: Bulletin of Lying-in Hospital, New York, 1911-1912, 
VIII, 16. 

Martin: Ztschr. f. Geburt. u. Gyilak., 1885, II, 416. 

Mauriceau: Traite des Maladies des Femmes Grosses, 6th Edi- 
tion, 1721, pp. 86-91. 

Mayer: Beschreibung einer Graviditas interstitialis uteri, nebst 
Beobachtungen iiber die merkwiirdigen Veranderungen welche die 
weiblichen Genitalien und namentlich der uterus in hohen Alter 
erleiden, Bonn, 1825. 

Maygrier: Zntralbl. f. Gynak., 1908, XXXII, 84. 

Nacke: Zntralbl. f. Gynak., 1911, XXXV, Nr. 38, p. 1345. 

Oastler: American Journal of Obstetrics, 1915, LXXII, 1044. 

Opitz: Ztschr. f. Geburt. u. Gynak., 1899. XL, 522. 

Pegaitaz. These de Geneve. 

Polak: Amer. Jour, of Obstetrics, 1910, LXII, 484. 

Popoff: J. Akush. i. jensk. boliez, St. Petersb., 1914, XXIX, 533- 
544. 

Robins: N. Y. Med. Journal, 1912, LXXXXV, 337. 

Schenk: Inaug. Dissert., Jena, 1913, F. Gobert, 42 p. 8°. 

Schmitt: Beobachtungen Kaiserl. Koenigl, Med.-Chir. Akad., 
Wien, ISOl. Band I, Theil 5. 

Schumann: Amer. Jour, of Obstetrics, 1912, LXV, 591. 

Scott; Amer. Jour, of Obstetrics, 1911, LXIV, p. 821. 

Siefart: Zntralbl. f. Gynak, 1913, XXXVII, 375. 

Simon: Inaug. Dissert, Berlin, 1885. 

Steffen; Zntralbl. f. Gynak, 1908, XXXII, p. 892. 

Stumidort: Amer. Jour, of Obstetrics, 1910, 313. 

Viannay: Loire med., St. Etienne, 1913, XXXII, 410. 

Vineberg; Amer. Jour, of Obstetrics, 1915, LXXI, 810. 

Ward: Ibid.. 1913, LXVII, 1007. 

Weinbrenner: Ztschr. f. Geburtsh. u. Gynak, 1904, LI, 58. 

Werth: Handbuch der Geburtshulfe, Von Winckel. Zweiter 
Band., Theil II, 1904, S. 739 and S. 940. 

Wimmer: Zntralbl. f. Gynak., 1903, XXVII, 52. 



TRANSPLANTATION OF THE TRACHEA 

By Walter C. Borket, M. D. 
{From the Surgical Hunterian Laboratory of The Johns Hopkins University) 



With the pur]iose in view of the possible utilization of a 
tracheal transplant in human cases in which a portion of the 
trachea has been resected on account of malignant disease, as 
suggested by Dr. William S. Halsted. I undertook to study the 
transplantation of the trachea in dogs. And furthermore, as a 
I>rcliminary step in this problem, it seemed clear that an im- 



portant factor in the success of the tracheal transplants would 
be the determination of the sterility of the trachea at different 
levels. 

A review of the literature showed the rather extensive work 
that has been done on the healing of tracheal wounds after 
resection and the use of various grafts for closing tracheal 



JOHNS HOPKINS HOSPITAL BULLETIN 



Xo. :524 



<lefects. The work began in 1831, when Dupuytren first studied 
the phistic closure of the tracheal wall. In 1845 Deflfenbauch 
attempted to cover tracheal defects with a flap of tissue ; Schiil- 
ler in 1880 described the healing process of the tracheal 
wounds ; and it has been well known that the trachea could be 
completely divided and the ends successfully resuturcd in ani- 
mals and human cases, following a report of the work of Glutk 
and Zeller in 1881, and the later reports of Kiister, v.on Colley. 
Fiidcrl, vol! Eiselberg, Jones, Keene, Mesuard. von Hacker. 
Frankenberger, Frank, Gluck, Koenig, Kauder, von !v"avratil. 
N'owakowski, Turner, Alagna and Sarguon. Complete annular 
^^egments of the trachea, varying in length from 2 to 5 cm., 
were excised and the remaining tracheal stumps success- 
fully sutured by Kiister in 188.5, Nowakowski in 1909, and 
Alagna in 19 J 3. By far the greater portion of study lias 
been applied to the treatment of tracheal fistukv, by using 
various materials for transplantation. In 1893 Photiades and 
fjardy used a .skin-jieriosteal cartilaginous flap from the clav- 
icle; while Schimmelbusch in 1893, Koenig in 1897, Aue in 
1900, and Kusnetzow in 1909, reported using such a flap from 
the sternum; a skin and thyroid cartilage flap was u.sed by 
Koenig in 189G and by Wiessinger in 190(5 ; a rib cartilage flap 
I)y von Mongold in 1899, and by Mehues in 1903 ; a periosteal- 
cartilage flap from the tibia by von Xavratil ; a silver wire net 
l)y Grosse in 1901; free fascia transplants by Kirschner in 
1910; and fascia lata by John Staige Davis in 1911. Tjater 
reports of studies with the iise of fascia iiave been made by 
Koenig, Holimeier, Kostenko, Rubasckew, Levit, Lucas, 
Kirschner, Miinnich, Jacquin and Malan. Various methods 
of using skin flaps from tiie neck have been described by 
Trnka and von Masek. In 1893 Photiades and Lardy used a 
rubl)er tube surrounded l)y a skin flap to take the place of a 
tracheal defect following a resection of the trachea for cancer. 
Lazarraga, Firniin-Gaston l?ouzoul, Baraez and Bruwer have 
gone over part of the literature upon jdastie surgei-y of tbr 
trachea. But searching through the literature revealed no 
other aid in the present ])roblem until it inul been colnpleted, 
when the re))orts of three dill'ereiit authors were found whicb 
have been comjiletcly aiistractcd in tbc I'lillowing paragra|ili: 
Mesnaril in I '.MM reported before the Anatomical Soeietv ul' 
Paris that I'luir days previously he had begun the studv ni' 
transpbintatioi) of cnniijlete segments of the trachea in two 
dogs, and tlia* he W(inid show the results at the ne.\t meeting 
of the society; Init there was no subsetpient statement of the 
outcoino of this attempt that could lie found. The second ex- 
perimenter was Caldera. ulm. in 1913, reported three groups 
of experiments on ralibits. lie successfully resutured witii 
catgut the divided trachea, and at post-mortem examination 
found a well-iieaU'd wound tbat I'drinetl a clearly marked an- 
nular scar which was infiltrated with calcai-eous salts. In the 
second group of experiments Caldera made tracheal transplants 
of complete segments, 1.5 cm. in length, with the result that 
one rabbit had post-operative .-iymptoms of stenosis for 16 days, 
and post-mortem examination after 20 days showed a heavy 
annular deposit of calcium salts, while another rabbit showed 
a calcarcons indltration of the cicatrix wit!i<uit stenosis. In 



the third group of experiments he made tracheal transplants 
of segments of similar size after preserving theihjor 2-1 and 
48 hours in sterile Ringer's solution at 37° and 20° C., res- 
pectively. He reported at the end of 20 days a satisfat^torv 
clinical and anatomical result and a moderate calcereous infil- 
tration of the cicatrix without stenosis. In conclusion he 
stated, without having made any cultural examinations that 
one could find, that the bacteria which were habitually present 
in the trachea had become attenuated in virulence, so that 
therefore they did not constitute a danger at the time of the 
operation. Furthermore, he added that the anastomotic union 
of the trachea took place by connective tissue, which was infil- 
trated with lime salts. He mentioned no bibliography and 
only briefly described his specimens, which were not reproduced 
in the article. Finally, Zuccardi-Merli in 1914 reported an 
experiment upon dogs in which he planned to repeat the work 
that Caldera did upon rabbits. Losing the same technique he 
tried fresh tracheal tran.«plants consisting of four cartilagenous 
rings, with the result that a left lateral stricture was formed 
that did not produce symptoms during life. In the case of 
the transplants preserved for 48 hours in Ringer's solution and 
•placed in a different-sized animal, be claimed to have obtained 
after 20 days a satisfactory union without stenosis. He then 
repeated the fresh tracheal transplants of the same diameter 
of the trachea aiul employed more accurate technique, witli tlie 
result that all were failures. He stated that the stenosis, which 
some observers have obtained after simple resection and suture, 
might be due to the contraction of an organized blood clot 
about the trachea, as a result of the imperfect approximation 
of the bleeding edges. He did not fully describe the si)ecimens, 
which were not reproduced in the article. 

On account of the splendid results obtained in several of the 
cases of auto-tracheal transplants in dogs, it was deemed ad- 
visable to report the following experiments which seemed to 
divide themselves into two classes ; the main division consisted 
in the auto- and iso-transplantation of complete annular seg- 
ments of the trachea in dogs ; and a subordinate division, which 
was undertaken as a preliminary step to the nuiiii problem, 
consisted in the determination of the sterility at different levels 
of the trachea of the cat. 

The experiment to determine the sterility of the trachea was 
as follows: Under ether ana'thesia and after sterilizing the 
operative field thoroughly with alcohol, tiie trachea was ex- 
posed from the larynx to its bifurcation. Blood for cultures 
was taken from the carotid artery. Four sets of sterile instru- 
ments were used in obtaining the ditferent specimens, as fol- 
lows: One to expose the tracliea and to remove wound musck 
as control culture of the operative technique; and other sets 
to remove the trachea at three different levels; that is, at the 
bifurcation, midway up, and just below the larynx, respectively. 
These tracheal rings and iiieees of muscle were placed in broth, 
in Ringer's solution, in blood, and in 1/100000 aqueous bichlor- 
ide solution. Some of the cultures were kept on ice and others 
at 37° C. Approximately fiO cultures were thus made. All of 
the control cultures and all t]ie cultures that were kept on ice 
an<l later placed in the thermostat remained free f nun bacterial 



FKnTit-AnY. 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



growth, as did also the cultures that were kept at 37° C, -except 
for a cloudy growth after 48 hours in oue of the broth cultures 
from the trachea near the hilus of the lung, which contained a 
small piece of a lymph gland that probably accounted for the 
iiPowth. The stained smear of tliis culture showed a Gram- 
positive coccus that was not in chains. The remaining cul- 
tures of the trachea near the hilus of the lung showed no 
i;rowtll. 

Witli a knowledge of the preliminary facts as just stated 
concerning the sterility of the trachea, the following experi- 
ment in the auto-transplantation of the trachea in dogs was 
made. The animals were kept under ether an;psthesia by 
mouth or through a tracheotomy wound. .V midline incision 
was made from the larynx to the suprasternal notch and the 
muscles separated down to the pretracheal fascia. This fascia 
lontained numerous blood vessels, which in part supplied the 
circulation to the intercartilaginous portions of the trachea. 
These vessels were ligated and divided only over that portion 
of the trachea which was to be transplanted. A second im- 
jjortant blood supply of the trachea was furnished by a vessel 
upon either side of the trachea and parallel with it; this was 
ligated just at the point where the trachea was to be divided, 
in order to preserve the circulation of the trachea to the very 
line of incision. After careful attention to the blood supply, 
a segment of the trachea, composed of from three to nine car- 
tilaginous rings in length, was completely separated by trans- 
verse incision and removed, thus assuring complete absence of 
blood supply to the transplant. This auto-transplant was then 
replaced and sutured end-to-end by using three equidistantly 
placed interrupted black silk sutures, which picked up the 
])erichondriuni and cartilage without penetrating the entire 
tracheal wall. The silk was threaded' on fine, curved French 
needles which were fastened in a needle-holder, and very small 
delicate forceps were used to steady the tissues in order to avoid 
trauma. One short continuous black silk suture was placed in 
the fibro-elastic posterior wall of the trachea. Both ends of the 
transplant were sutured in the same way. The incised end of 
the transplant was just approximated to the cut surface of the 
trachea, without tension or overlapping. No disfigurement to 
the normal contour of the trachea was caused by the trans- 
plant, and no air escaped through the line of anastomosis 
when it was completed. One long heavy black silk tension 
suture (refer to photograph) was placed in the anterior sur- 
face of tire trachea from above to below the transplant in order 
to relieve tension upon it during the process of healing. The 
perichondrium of the tracheal rings proved to be the strong 
layer of closure. The pretracheal fascia was approximated 
with a continuous silk suture; the muscles were brought to- 
gether in the midline; and the skin was tightly closed with a 
continuous subcuticular fine black silk suture. A collodion 
gauze dressing was applied. 

The operative technique in the cases of the iso-trachcal 
transplants was similar to that just stated for the autotrans- 
plants. Both animals were operated upon at the same time 
and the tracheal transplants were interchanged. Intratracheal 
ansBsthesia was administered through a separate tracheotomy 



wound which was located below the region of the transplant. 
It was an interesting fact that the tracheal segments from the 
different-sized animals were readily adapted in size to one 
another because of the anatomical fact that the cartilaginous 
portion of the tracheal rings was not complete and the posterior 
wall was formed of fibro-elastic tissue. 

All animals recovered promptly from ana'sthesia and oper- 
ation. The skin wounds healed per primam. After operation 
some of the animals (C„ C^, C„ D^, D,) had an hoarse voice, 
a dry cough, and a rather stiff neck, which, when walking, they 
would occasionally shake from side to side, especially in the 
case of the dogs with the long transplants. Although otherwise 
their general condition remained very well, yet after from one 
to three weeks they developed marked symptoms of tracheal 
obstruction with dyspntea, and died. Autopsy revealed a nor- 
mal esophagus and lungs, and a stricture of the trachea at the 
site of the transplant. Only one animal (CJ developed a 
purulent infection at the site of the transplant, together with 
a complicating bronchitis and pneumonia which caused death 
in four days after the operation. In these unsuccessful cases, 
the dogs with the short tracheal transplants lived from one to 
two weeks, while the animals with the long transplants lived 
approximately three weeks. The eases of iso-tracheal trans- 
plants resulted in death with symptoms similar to the unsuc- 
cessful cases of auto-transplants, and autopsy showed normal 
lungs with stricture of the trachea at the region of the trans- 
plant. 

The microscopical studies of sections made through the an- 
terior and posterior walls of the strictures showed it to consist 
of a mass of granulation tissue, in the deeper layers of which 
there were pieces of poorly staining cartilage that were in the 
process of destruction. Many long and short chains of a rather 
large, thick bacillus and numerous scattered cocci were present. 
The mucous lining was iisually absent and the normal relation- 
ship of the tracheal layers was destroyed. 

The successful transplant cases {C3, C-, C^) showed no 
symptoms and gave every evidence that they were as healthy 
and normal as before operation. At the time when these dogs 
(C3, C5, Cg) were sacrificed in order to observe the experi- 
mental results, hair had grown out and coyered the neck of the 
animal, completely hiding the white line of the operative in- 
cision. The neck showed nothing unusual in appearance, and 
upon palpation the structures of the neck felt normal and were 
freely movable. Upon exposing the trachea it was found 
normally mobile, without adhesions, and one could make out 
by gross examination no reaction in the tissues or structures 
about the site of the transplant. The healing was so satis- 
factory that the location of the anastomosing silk suture was 
the best guide to the transplant. There was no disfigurement 
to the normal contour of the trachea, as can be seen in the 
photographs which were taken by J. A. Martin, of the Johns 
Hopkins Hospital. The color, consistency, and shape of the 
cartilage and tissues forming the transplant seemed normal, 
like that in the unoperated portion of the trachea. The inside 
of the trachea was smooth and normal throughout its length. 
The life of the.se perfect transplants (C^. C„ C^), that is, from 



38 



JOHNS HOPKINS HOSPITAL BULLETIN 



[Xo. 32 1 



the date of the operation until the animals were sacrificed, 
was 63, 54, and 36 days, and the segment transplanted was 
composed of three, four, and seven cartilaginous rings, 
respectivel)'. 

Upon histological examination of the anterior and pos- 
terior walls of the trachea, the tissues of the transplant ap- 
peared so normal that it was diflScult to locate the point of 
anastomosis except by the presence of the suture or by the 
knowledge of the location of the section in the original speci- 
men. The layers had their normal relationship. The epithe- 
lium was everywhere present, although it was not as high at 



little indenture on the left side of the transplant which proved, 
on opening the trachea, to be a moderate lateral stricture. 

Therefore, from the above facts one might say: (1) that 
according to the studies with cultures, the trachea was prac- 
tically in all cases sterile from the larynx to the hilus of the 
lung; (2) that transplant C^ — 54 days, was an example of a 
perfect auto-tracheal transplant; (3) that in the successful 
cases the healing took place by the normal layers of the tracheal 
wall and not by fibrous cicatrix; (4) there was no infiltration 
with calcareous salts; (5) that the strictures resulted from an 
infection which was caused bv the orsfanisms that were observed 



RESULTS OF TEACHEAL TRANSPLANTS— ALL ANIMALS REPORTED 



No. of 

medium- Date of opera- 
or large- ! tion, 1917 
sized dog 



C, March 31. 



C» I April 17. 



April 18. 
April 19. 



Cj April 2(5. 
Co April 26. 

C; May 8. 



C, 



May 11. 
May 25. 
May 25. 



No. of 

tracheal Auto- oi 
rings iso-trar.B 
trane- | plant 

planted : 



Post-Operative symptoms 



End of 
experiment 



Per priraain. 



Slight hoarsness, slight stiff- 
ness of neck. Tendency to 
shake neck. After 10 days 
difliculty in breathing began 
and became gradually fatal. 

Slight dry cough for a few- 
days. 



(Xone) 



Infection at DitliciiHy in breathing. Rapid, 
site of trans- short respiration. Some 
plant. prostration at end. 



Per primaii 



(Xon.') . 



Neck somewhat stiff. Shakes 
head and neck. Voice hoarse. 
Some difficulty in respira- 
tion. 



(Xonel . 



Difficulty in respiration. Dry 
cougli. 

Difficulty in r^-spiration. Dry 
cough. 



Died. 

April 14. 



Sacrificed. 
.June 19. 



Sacrificed, 
June 19. 



Died, 
April 2.S. 



Sacrificed. 
.June 19. 



Saoriliced, 
June 19. 



Died, 
June 2. 



Sacrificed, 
June m. 



Died, 
.lune 2. 



Died. 
June 1. 



Duration of 
experiment 



14 days. 



Stricture of trachea. Lungs 
OK. 



ti3 days. I .Slight stricture on left side of 
trachea. Lungs OK. 

02 days. Transplant fine. Lungs OK. 



4 days. Breaking down of transplant; tj 

bronchitis; pn'eumonia. ' 



54 days. Transplant perfect. Lungs OK. 



24 days. Stricture of trachea. Lungs 

OK. 



25 days. Stricture of trachea. Lung 

OK. 

36 days. Transplant fine. Lungs OK. 

8 days. Stricture. 

7 days. Stricture. 



the point where the incision had been made. The anastomosis 
was formed by the tissues of the different layers themselves and 
not by connective tissue. There was no scarring or infiltration 
with lime salts. There was no reaction in the tissues except 
for a beginning giant-cell development about the sutures which 
took place for the purpose of absorbing the silk. The cartilage 
of the transplant stained the same and, as nearly as one could 
tell, resembled that of tlie untransplanted portion of the 
trachea. No bacilli nor cocci could be seen anywhere in the 
sections. 

A fourth case (C^) had a slight dry cougli for a few days 
after operation, which cleared up. Otherwise, dog (C,) seemed 
healthy and normal and when sacrificed G3 days after opera- 
tion, the trachea looked to be in good condition except for a 



in the histological sections: (fi) that i.*o-traelieal transplants 
resulted in stenosis. 

Furthermore, one might offer an explanation or possible 
interpretation of several facts which became evident in the 
course of these experiments. In the first place, tlie stricture 
of the trachea that resulted in the unsuccessful cases was 
probably due to the low-grade infection that was not sufficiently 
virulent to cause the skin wounds to break down or to infect 
the lungs. The organisms might have gotten into the trachea 
Vith the air while the animals breathed through the tracheot- 
omy wound at the site of operation. A second point that per- 
haps might be mentioned was that the infection which appeared 
in the one tube containing the ]iiece of lymph gland, during 
the study of the sterility of the trachea, emphasized the point 



Eebruaey, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



39 



that lymphatic vessels and glands which must be cut across in 
a clean wound sliould receive careful sterilization either with 
the cautery or by carbolic-alcohol technique, Just as any other 
infected material. This would be especially true in a case where 
the o-lanJs and vessels drained regions that were known to be 
badly exposed to infection. Such techniqiie would only require 
a more accurate knowledge of the Ijinphatic structures and 
their drainage, and cutting these infected lymphatic vessels 
and glands might explain some of the unexpected infections 
wliieh develop in clean wounds. 

I wish to acknowledge the help of Dr. Joseph Lawrence, of 
the Bacteriological Department of the Johns Hopkins Univer- 
sity, in making the tracheal cultures. 

BIBLIOGRAPHY 

1880, Schiiller, M.: Heilungsprocess der Trachealwunde. Deut- 
sche Chir., 1880, XXXVII, 96-100. 

1881, Gluck, T., und Zeller, A.: Die prophylaktische Resektion 
der Trachea. Arch. f. klin. Chir., Berl., 1881, XXVI, 427-436. 

1888, Noll, F. W. : Ein Fall von Abtrennung der Luftrohre vom 
Kehlkopf bei fast unversehrten ausseren Weichtheilen durch 
Operationen u. s. w., erzielte vollstandige Anheilung. Deutsche 
Ztschr. f. Chir., Leipz., 1888, XXVII, .597-600. 

1893, Kiister: Zur Deckung von Trachealdefekten. Verhandl. d. 
deutsch. Gesellsch. f. Chir., Berl., 1S93, XXII, 80-81. 

, Schimmelbusch: Zur Deckung von Trachealdefekten. 

Verhandl. d. deutsch. Gesellsch, f. Chir., Berl., 1893, XXII, 78-80. 

, Photiades u. Lardy: Contributions a la chirurgie des voles 

respiratoires. Rev. med. d. la Suisse, rom., Geneve, 1893, XIII, 
44-50. Ref.: Zentralbl. f. Chir., Leipz., 1893, XX, 895. 

1894, Colley, F.: Die Resektion der Trachea; eine experimen- 
telle Studie. Deutsche Ztschr. f. Chir., Leipz., 1894, XL, 150-162. 

1896, V. Eiselberg, A.: Zur Resektion und Naht der Trachea. 
Deutsche med. Wchnschr., Berl. & Leipz., 1896, XXII, 343-344. 

, Koenig, F.: Zur Deckung von Defecten in der vorderen 

Trachealwand. Berl. klin. Wchnschr., 1896, XXXIII, 1129-1131. 

, Foderl, O.: Zur Resektion und Naht der Trachea. AVien. 

klin. Wchnschr., 1896, IX, 1258-1260. 

1897, Koenig, F., u. Konig, Jun,: Ersatz eines grossen Tracheal- 
defektes. Verhandl. d. deutsch. Gesellsch. f. Chir., Berl., 1897, 

XXVI, 95-102. 

1899, V. Mangold: Ueber die Einpflanzung von Rippenknorpel 
in dera Kehlkopf zur Heilung schwerer Stenosen und Defekte. 
Arch. f. klin. Chir., 1899, lix, 926-936. Ibid., 1900, LXI, 955-969. 
Verhandl. d. deutsch. Gesellschatt. t. Chir., 1900, 460. 

, Jones, N. S., and Keen, W. W. : Two unusual cases of 

surgery of the trachea. Phila. M. J., 1899, III, 1295-1298. 

1900, Aue, G. K.: Plastische Deckung von Trachealdefekten. 
Arch. f. klin. Chir., Berl., 1900, LXI, 124-129. 

. Trnka: Eine praktische Methode der Tracheoplastik mit 
gedoppeltfcu Hautlappen. Zentralbl. f. Chir., Leipz., 1900, XXVII 
413. 

, Mesnard, M. A.: Pieces de suture de la trachee de chien. 
Bull. Soc. anat. de Par., 1900, LXXV, 1037. 

, Mesnard, A.: Sutures de sections completes de la trachee 
f-liez des chiens. Bull. Soc. anat. de Par., 1900, LXXV, 1070. 

1901, V. Hacker: Resektion der Luftrohre mit primarer zirku- 
larer Naht wegen hochgradlger rlngformiger Narbenstriktur; 
Idee einer halbseitiger Laryngoplastlk. Beitr. z. klin. Chir., 
Tubing., 1901, XXXII, 709-724. 

, Frankenberger, 0.: Sur la resection de la trachee. 

Transl.: Ann. d. mal. de roreille, du larynx (etc) Par 1901 

XXVII, 424-436. 

, Grosse: Trachealknorpel Defekt und silberdraht Netz 

Bedeckung. Zentralbl. f. Chir., Leipz., 1901, XXVIIl, 1110-1111. 



, Baracz: Ein Beltrag zur Tracheoplastik. Transl.: Wien. 

klin. Wchnschr., 1901, XIV, 1054-1056. 

1902, Prank: Ueber Trachealstenose und deren Behandlungs- 
methoden. Inaugural Dissertation, Bonn, 1902, 8°, p. 47. 

, Gluck T.: Der gegenwartige Stand der Chirurgie des 

Kehlkopfes, Pharynx und der Trachea. Chirurgenkongress, 1902. 
Zentralbl. f. Chir., Leipz., 1902, XXIX, 64-67. 

, V. Hacker: Kontinuitats Resektion der Trachea und cir- 

culare Naht. Wien. klin. Wchnschr., 1902, XV, 829. 

1903, Kander: Resektion und Naht bei Tracheal- und Diaphragm- 
Larynxstenose. Beitr. z. klin. Chir., Tiibing., 1903 XXXVIIl 
133-149. 

, Mehues: Ueber die Behandlung von Larynxstenosen und 

Trachealdefekten— Sitzung der freien Vereiningung der Chirurgie, 
Berlin. Zentralbl. f. Chir., Leipz., 1903, XXX, 846. 

, V. Navratil: Pall von Trachealstenose geheilt mlttelst 

Transplantation eines Hautperiostknochenlappens. Pest, med.- 
chir. Presse; Budapest, 1903, XXXIX, 452-453. 

1904, V. Eiselberg: Zirkulare Resektion der Trachea wegen 
Karcinoma der Schilddriise. Wien. klin. Wchnschr., 1904, XVII 
580. 

, V. Hacker: Ueber die Behandlung der Narbenstrikturen 

der Luftrohre und die Mangold'sche Laryngo-Trachealplastik. 
Beitr. z. klin. Chir., Tiibing., 1904, XLIV, 762-786. 

, V. Masek: Ein Fall von Operation einer Trachealflstel. 

Zentralbl. f. Chir., Leipz., 1904, XXXI, 27. 

1906, V. Hacker: Schleimhaut und Knorpelplastik bei Stenose 
der Luftrohre infolge von Sklerom. Wien. klin. Wchnschr., 1906, 
XIX, 1508-1512. 

, Wiessinger: Aerztlicker Verein in Hamburg. Sitzung 

vom 12 December, 1905. Miinchen. med. Wchnschr., 1906, LIII, 46. 

1908, V. Navratil, D. : Ueber die zirkulare Trachearesektion ; 
eine neue Tracheanaht. Deutsche Ztschr. f. Chir., Leipz., 1908, 
XCIX, 450-460. 

, Firmin-Gaston Rouzoul : Camelards et tracheaplastic. Bor- 
deaux, 1908, 39 pp., 8°.* 

1909, Turner, G.: Resection of the trachea for cicatricial stenosis. 
Brit. M. J., Lond., 1909, I, 1355. 

, Kusnetzow, M. M.: Die operative Behandlung von Defekten 

und Stenose von Kehlkopf und Luftrohre. Zentralbl. f. Chir., 
Leipz., 1909, XXXVI, 589. 

, Nowakowski, K.: Beitrag zur Tracheoplastik. Arch. f. 

klin. Chir., Berl., 1909, XC, 847-861. 

1910, Kirschner, M.: Die praktischen Ergebnisse der freien 
Pascien-Transplantation. Verhandl. d. deutsch. Gesellsch., f. Chir., 
Berl., 1910, XXXIX, 223-247. 

1911, Davis, John Staige: The transplantation of free flaps of 
fascia; an experimental study. J. H. H. Bull., Bait., 1911, XXII, 
372-381. Ann. Surg., Phila., 1911, LIV, 735-749. 

, Koenig: Neue Wege der plastischen Chirurgie. (Verlotung 

und Ueberbrachung). Verhandl. d. deutsch. Gesellsch. f. Chir., 
Berl., 1911, XL, 92-110. Berl. klin., 1896. Arch. f. klin. Chir., XCV, 
Deutsch. med. Wchnschr., 1911, 150. 

, Hohmeier, P.: Experimente iiber Verschluss von Wunden 

und Ueberbriickung von Defekten Schleimhautragender Korper- 
canale und Hohlen durch freie Autoplastik. Verhandl. d. deutsch. 
Gesellsch. f. Chir., Berl., 1911, XL, 124-134. Arch. f. klin. Chir., 
191, XL, 345-358. 

, Hohmeier, P.: Ueber ein neues Verfahren zur Deckung von 

Trachealdefekten. Miinchen. med. Wchnschr., 1911, LVIII, 948. 

, Lazarraga, J.: Beitrag zur Tracheoplastik. Griefswald, 

1911. 

1912, Kostenko u. Rubasckew: Ueber die freie Fascientransplan- 
tation. Zentralbl. f. Chir., Leipz., 1912, XXXIX, 1448-1449. 

, Levit, H.: Deckung von Trachealdefekten durch eine freie 

Plastik aus der Fascia lata femoris. .\rch. f. klin, Chir,, Berl,, 
1912, XCVII, 686-699, 



40 



JOHXS HOPKINS HOSPITAL BULLETIN 



[>^'' 



1913, Lucas, H.: Ueber die freie Plastik der Fascia lata. Arch, 
f. klin. Chir.. Berl.. 1913, C, 1129-1136. 

^ Kerschen. M.: Der gegenwartige Stand und die nachsten 

Aussichten der autoplastischen freien Fascien Uebertragnng. Beitr. 
z. klin. Chir., Tiibing.. 1913. LXXXVI. 5-149. 

, Gluck: Fall von totale Exstirpation der Trachea. Verof- 

fenU. d. Hufeland. Gesellsch. in Berl.. 1913, iS. (Discussion. 30 i. 

, Glnck: Totale Exstirpation des Trachea zur Bifurkation. 

Berl. klin. Wchnschr.. 1913. 1. 2105. 

, Alagna, G.: Zur zirkularen Trachearesektion ^ De-.tsche 

Ztschr. f. Chir., Leipz.. 1913, CXXV, 613-615. 

, Brewer. G. K.: Repair of tracheal wou:. ■-»- 

Keen's Srstem of Surgery, 1913, TI, 366-36S. Ibic.; ly.'S, III, 

510. 



, Caldera, C: Chirurgia sperimentale della trachea. Arch. 

ital. di otol. (etc.) , Torino, 1913, XXIV, 21-24. 

1914, Jacquin: Deckung eines Trachealdefekts dorch einen 
freien Fascienlappen aus der Fascia lata. Deutsche med. Wchn- 
schr., Berl., u. Leipz.. 1914, XL, SSI. 

, Munnich: Ueber die Deckung von Trachealdeftokten ver- 

mittelst autoplastischer freier Fascientransplantation. Deutsche 
Ztschr. f. Chir., Leipz., 1914, CXXVI. 193-200. 

, Sarguon: Tracheo<ricostomie pour stenose cicatricielle 

du cricolde. Lyon med.. 1914, CXXIII, 106-109. 

, Zuccardi-Merli: Contributo alia questione die trapianti 

tracheale. Arch. ital. di otol. (etc.), Torino, 1914, XXV, 190-192. 

1915, Malan, A.: Trapianti liberi di fascia lata per riparazione 
di perdite di sostanza della trachea. BoU. d. mal. d. creschio. d. 
gola. ed. naso.. Firenze, 1915, XXXIIl. 177-189. 



EXPERIMENTS IN THE ARTIFICIAL PRODUCTION OF AMYLOID 

By K. Htbose 
{,From the Department of Pathologjf of The Johns Hopkins University) 



\ / xplanations of the arterial hypertension that 

iritis are veni- unsatisfactory, the fact that 
amv...:,i ,;iM;is<- of the kidney is almost always without eSecx 
upon the blood pressure and without an accompanying hyper- 
trophy of the heart is one of great interest. 

At the suggestion of Drs. Welch and Wintemitz, the : 
lowing experiments were imdertaken with the object of 
dneing amyloid artificially in the kidneys of animals, in . : 
to determine whether it is really true that amyloid kidtc. ? 
are unassociated with high blood pressure and to study the " j 
effects of vasoconstrictor and vasodilator influences in ?- 
animals. The experiments failed of their object, how 
inasmuch as it was found impossible to produce amyloiu 
any of the methods employed. Nevertheless, the publication | 
of a brief summary of the work seems justified be<:-au>e - 
shows that, even when the methods described by other wr 
are faitlifully followed over long periods, amyloid may i.-.i [ 
to appear, a fact which would suggest that its oc-c^sional 
development must be regarded as either accidental or due to 
some factor not definitely recognized. 

Notwithstanding the prolonged efforts of many •• ■ ^- ^ 
tors in past years, there is no recognized way in whi. 
can be uniformly produced in the animal botly. 

Positive results have beeh obtained in the rabbit, dog, mouse, 
horse and hen by the following: In the rabbit, by Bir ' 
Hirschfelil, Bouehard-Charrin, Condorelli-Mangeri. Kraw; 
Maximow, Davidsohn, Lubarsch, Xowak, Sczegolew, Eauu :- 
sehek. Schepilewskv- and Dantschakow. In the dog by Czemy 
and Lubarsch. T - •' by Davidsohn and F— ■ ^■ 

the Aorsff by Ze: -.d Peare*. Lewis, Sch. 

and Markus. In tiK- i^'n i'\ Krawkow. Maximow. I'in ;•;?•■;;.; 
and Xowak. 

^' . results were obtained in experiments with the ' 

an : with the guinea-pig by Gianturco, David> 
Lurtiir- a and Tarehetti : with the dore and frog by Kraw 

In order to produce amyloid, all of the investigators 
injections of var - - ' ".nc-es into the animal. The >!.■ 
stances which j oid are as foUows: 



Staphylococcus a^treus (Condorelli, ilangeri, Krawkow. 

Maximow, Lubarsch, Xowak, Davidsohn, Sczegolew, Raubit- 

sohek, Dantschakow), B. pyocyaneus (Bouchard, Charrin. 

Krawkow. Xowak, Michailowitsch), B. coU (Xowak, Baily). 

P. termo (Condorelli, ilangeri), Friedldnders bacillus 

Frank), Gonococcu.? (Davidsohn), J5. <uiprcu/osi^( Bouchard. 

rrin). B. dysenteri<e (Marktis), B. pesti^ ( Schoukewitsch ) , 

refactive bacteria (Sowak), Fresh and sterile pus, (Birch- 

.iimiifeld, X'owak). Oil of fHr/jen/iiie (Czerny,"Enbarsch. 

Xowak. Sczegolew), Various ferments (Schepilewskv), Di/>7<- 

''■Tia toxin (Zenoni, Pease, Pearce, Lewis). 

the streptococcus (Davidsohn, Lubarsch), pneumococcu.< 
, Lubarsch), tetanus toxin (Pease, Pearce), tuberculin (Xo- 
wak). croton oil (Xowak) and silver nitrate (Krawkow) were 
"'^ used, but gave n^ative results. 

Not all of these substances were used for any one animal. 
L.ut c-ertain ones for certain animals, as follows: 

Rabbit: Pus, B. pyocyaneus, B. tuberculosis. Staphylococ- 
cus aureus, B. c-oli, oil of turpentine, ferments, sterile filtrate 
of B. pyocyaneus. Dog: Oil of turpentine. Mouse: Staphy- 
I. ,^ . „,^..,;^ gonococeus, Friedlanders bacillus. Horse: 
xin, B. dysenteri*, B. pestis. Hen: Staphy- 
in^.nK- o^wius: B. pyocyaneus. sterile filtrate of Staphylococ- 
cus aureus and B. coli, putrefied bouillon, pus, sterile ptvs, 
"■'. of turpentine. 

Some substances produced amyloid in certain animals and 

uoi in others. For instance. Staphyloc-occus aureus gave a 

negative i^ult in the dog. guinea-pig. cat. dove and frog 

Krawkow, Davidsohn. Lubarsth, Petrone, Tarehetti) : B. 

waneus and cholera bacillus in the hen (Krawkow) : the 

rv.leil B. pyocyaneus and FrietUanders bacillus in the guiD«»- 

pig (Lubarsch); oil of turpentine in the guinea-pig <Tar- 

hotti) ; putrefied bouillon and sterile ptis in the raW»it (Xo- 

;ik) : B. coli in the hen (Xowak) : and sterile filtrates from 

Iture of Staphylococcus aureus in the rabbit (Krawkow). 

lertain investigators have obtained absolutely negative rc- 

^ults witli the same animals and substances which had shown 

positive results in the hands of previous experimenters. For 



February, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



41 



instance, Staphylococcus aureus failed to produce amyloid in 
the rabbit (Petrone, Tarchetti) ; living B. pyocyaneus and 
B. coli in the rabbit (Nowak) ; suppuration in the rabbit 
(Gianturco) ; B. dysenteria; in the horse (Pease, Pearce) ; oil 
of turpentine in the dog (Krawkow). 

It may be seen from the foregoing that although many dif- 
ferent substances have been injected over long periods into 
several different types of animal, no constant success has 
attended upon these experiments. In this study, animals were 
chosen from the list of those already used with success, vfhich 
were suitable for the study of the blood pressure, and the 
methods of injection employed were those that had been most 
frequently successful. Goats, dogs and rabbits were used, 
Staphylococcus being injected into the rabbits and goats and 
oil of turpentine into the dogs. The use of Staphylococcus 
aureus was based on Krawkow's method, and cultures in bouil- 
lon, from three to seven days old, were injected under the 
skin of the back, twice a week, in increasing doses starting 
with 0.3 or 0.5 c. c. New strains of Staphylococcus were used 
whenever they could be obtained from human autopsies or 
elsewhere. Instead of the living cultures given subcutane- 
ously, killed cultures of Staphylococcus aureus were injected 
intravenously into a number of rabbits. The 48-hour bouillon 
culture was killed by heating in a water-bath at G0-G2° t'. 
for 20 minutes, and injections were made twice a week in 
increasing doses. The method of using turpentine in the dogs 
was based upon that of Lubarsch. Beginning with doses of 
0.5 c. c, it was injected subcutaneously into the back of the 
dog, the dose being increased gradually and marked suppura- 
tion maintained. 

The experiments were as follows : 

I. Three goats injected with living cultures of Staphylococcus 
aureus over periods of 225, 245 and 253 days received respectively 
629, 719 and 819 c. c. of the culture. At autopsy they showed no 
amyloid in any of their organs. 

II. Six dogs received subcutaneous injections of turpentine twice 
weekly in doses increasing from 0.5 to 4 c. c. over periods which 



varied from 16 to 272 days. The total amounts of turpentine 
received by the dogs which lived a long time were 44 c. c. during 
165 days; 72 c. c. during 189 days and 94.5 c. c. in one dog that 
lived 272 days. Although suppuration was continuous and some 
of the dogs showed albuminuria and casts, the autopsy revealed 
no trace of amyloid in any of the organs in any case. 

III. Thirty rabbits received subcutaneous injections of bouillon 
cultures of living Staphylococcus aureus twice a week in doses 
beginning with 0.3 c. c, but increased gradually until doses of 
20-25 c. c. were being given in many cases. The rabbits lived for 
different lengths of time after the beginning of the experiment 
but some survived large doses for 90-173 days, receiving a total, 
in some cases, of as much as 370 c. c. of the culture. A few showed 
albuminuria but not one developed a trace of amyloid in the 
organs which were thoroughly studied at autopsy in each case. 

IV. Twelve rabbits were similarly treated with intravenous 
injection of killed Staphylococcus aureus, one surviving 249 days 
and receiving 441.8 c. c. of the suspension. Others survived for 
periods varying from 23 to 173 days and received corresponding 
doses of the suspension. Two of them showed albuminuria but 
the organs at autopsy were, in every case, devoid of amyloid and 
indeed showed little departure of any kind from the normal. 

In the goats, there were no significant changes in the kidney 
except that in one case there was a certain amount of epithelial 
necrosis probably associated with the terminal peritonitis. In 
the dogs after turpentine injections there were generally no 
special changes in the kidneys, although some showed hyaline 
glomeruli, epithelial degeneration and infiltration with wan- 
dering cells. 

Similar changes were found in the kidneys of a majority 
of the rabbits and some presented even extensive scarring. 
Albuminuria and casts were found throughout the experiment 
in many cases. Focal necroses — abscesses in the liver and 
abscesses in the spleen and lung — were also found. 

Changes in the rabbits treated with killed staphylococci 
were much less marked than in those treated with the living 
organism but were of a similar character. These changes are 
evidently due to the direct action of the injurious agent 
employed in the experiment, since the animals were normal 



TABLE I— GOAT 



Date 


Experiment 
No. 


Animal 
No. 


Staphy- 
lococcus 


Age of 
culture 


No. of 

c. c. 
injected 


Dose (in c. c.) 


Length of life 

after 
tirst injection 


Length of life 

after 
last injection 


Method of 
injection 


Urinary changes 


Amyloid 


1/28/16 

2/4/l« 

2/18/16 


I 
II 
III 


I 
2 
3 


Living 


3-7 daya 
3-7 " 
3-7 " 


719.0 
819.5 
029. 3 


0.5-32.0 
0.5-30.0 
0.5-30.0 


245 days 
253 " 
225 " 


1 day 
I " 
1 " 


Subcutaneously 


Albuminuria for a few days 
Ne*g. 


Neg. 



TABLE II— DOG 



Date 


Experiment 

No. 


Animal 
No. 


No. Of c. c. of 
turpentine 
injected 


Dose (in c. c.) 


Length of life 

after 
first injection 


Length of life 

after 
last injection 


Method of 
injection 


Urinary changes 


Amyloid 


1/7/16 


IV 


1 


24.0 


1.0-4.0 


48 days 


1 day 


Subcutaneously 


Neg. 


Neg. 


1/14/16 


V 


2 


18.5 


0,. 5-4.0 


.33 " 


1 " 


" 


Albuminuria, casts 


" 


2/25/16 


VI 


3 


2.0 


0.5-1.0 


16 " 


4 " 


" 


Neg. 


" 


3/28/16 


VII 


4 


72.0 


0.5-4.0 


189 " 


2 " 


" 


" 


" 


4/27/16 


VIII 


5 


94.5 


0.5-4.0 


272 " 


2 " 


" 


Slight albuminuria 


" 


7/13/16 


IX 


6 


44.0 


0.5-4.0 


165 " 


2 " 


" 


Albuminuria 


" 



42 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 324 



TABLE III— EABBIT 



Date 



1/3/16 

1/19/16 

2/11/10 

3/8/16 

3/13/16 

4/11/16 

4/10/10 

6/19/16 

6/22/16 

8/9/16 

10/11/10 

10/13/16 

10/23/16 

11/3/16 

12/30/10 

1/22/17 

3/19/17 

3/19/17 

3/20/17 

3/19/17 

3/20/17 

3/20/17 

3/24/17 

3/24/17 

3/31/17 

5/1/17 

5/1/17 

5/5/17 

5/5/17 

5/5/17 



X 
XI 
XII 
XIII 
XIV 
XV 
XVI 
XX 
XXI 
XXIII 
XXIV 
XXV 
XXVI 
XXVIII 
XXIX 
XXX 
XXXV 
XXXVI 
XXXVII 
XXXVIII 
XXXIX 
XL 
XLI 
XLII 
XLI 1 1 
XLIV 
XLV 
XLVIII 
L 
LI 



16 

17 

26 

30 

31 

33 

36 

37 

44 

51 

52 

53 

54 

55 

56 

57 

58 

59 

60 

61 

64 

66 

67 



Living 



7 dayi 
7 " 
■7 " 
7 " 



a 

3 

3 

3 

3-7 

3 

3 

3 

3 
,3 
'3 

3 

3 

3 
3 
3 
3 
3 
3 
3 
3 
3 
3 



Xo. of 

injected 



26.1 
25.3 
41.8 
1.8 
70.3 
17.3 
153.3 
88.8 
1.35.8 
370.0 
98.8 
1.8 
4.0 
153.8 
3.3 
3.3 
224.3 
30.3 
102.0 
144.3 
12.3 
323.3 
23.3 
!57.3 
28,5 
158.5 
148,5 
15.5 
10.5 
21.8 



Dose (in c. c.) 



0.3-(i.O 

0.3-5.0 

0.3-6.5 

0.3-1.0 

0.3-10.0 

0.3-5,0 

0.3-17.0 

0.3-10.0 

0.3-13.0 

0.3-20.0 

0.3-13.0 

0.3-1.0 

0.3-2,0 

0.3-15.0 

0.3-1.5 

0.3-1.5 

0.3-18.0 

0.3-7.0 

0.3-12.0 

0.3-15.0 

0.3-4.0 

0.3-25.0 

0.3-6.0 

0.3-10.0 

0, .5-7.0 

0.5-20.0 

0.5-18.0 

0.. 5-5.0 

0.5-4.0 

0.3-6.0 



Length of life 

after 
first injection 



44 days 

41 " 

43 " 

10 " 

78 " 

40 " 

91 " 
08 " 

ill " 

173 " 

92 " 



13 
13 
84 
33 
53 
07 
25 
lOH 
28 
42 
32 
60 
66 
18 
15 
29 



Length of life 

after- 
last injection 



Method of 
injection 



1 day 



Subcutaneously 



Urinary changes 



Albuminuria, casts 



Neg. 

Albuminuria 

Neg. 



Albuminuria, casts 
Neg. 



Albuminuria 
Neg. 



Albuminuria 



Neg. 



•iliglit albuminuria 
Neg. 



^eg. 















TABLE IV— RABBIT 








Date 


Experiment 
No. 


Animal 
No. 


Staph.v- 
lococcufl 
aureus 


Age of 
culture 


No. of 
injected 


Dose (in c.c.) 


Length of life 

after 
first injection 


Length of life 

after 
last injection 


Method of 
injection 


Urinary changes 


Amyloid 


5/4/10 


XVII 


12 


Killed 


48 hours 


99.3 


0.3-13.0 


77 days 


2 days 


Intravenously 


Albuminuria 


Neg. 


5/26/16 


XVIII 


13 


" 


48 " 


441.8 


0.3-15.0 


249 " 


1 " 


" 


Neg. 


" 


5/20/10 


XIX 


14 


" 


48 " 


1.8 


0.3-1.0 


9 " 


2 " 


.. 


<. 


" 


H/4/16 


XXII 


20 


" 


48 " 


158.0 


0.5-14.0 


107 •' 


7 " 


.. 


>. 


" 


10/27/10 


XXVII 


35 


" 


48 " 


37.0 


0.3-8.0 


00 " 


1 •' 


" 


« 


<< 


1/31/17 


XXXI 


45 


" 


48 •• 


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XXXIII 


47 


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Albuminuria 


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Febuuauy, lins] 



JOHXS HOPKIXS HOSPITAL BULLETIN 



43 



iluring the early sta.ux'K of the experiment and only later began 
t(_i show allnniiiiiuria and easts. 

Other antliors, such as Xeisser and Wechsliero;, Stoddard 
and Woods, and Major, have' also found lesions in the kidney 
after the injection of cultures or filtrates from bouillon cul- 
tures of Staphylococcus aureus. Although Jackson and Le 
Count found spontaneous renal lesions in 11 out of 50 rabbits, 
Major, in examining a large number of normal rabbits, found 
that none of them showed such extensive changes as in thase 
sul)jected to the staphylococcus injections. 

Xo conclusions concerning the chief point of this problem 
can l)e reached from the present series of experiments, since 
no amyloid degeneration was produced, but it is at least shown 
that the artificial production of amyloid is very difficult and 
inconstant, even when methods are employed which have some- 
times been successful. Renal lesions are produced, it is true, 
but it appears that the factor responsil)le for the production 
of amyloid is as yet unrecognized. 

Ill conclusion, it gives me. great pleasure to extend my 
thanks to Drs. Welch and Winternitz for their many helpful 
suggestions and directions. 

1 also wish to thank Dr. Bayne-Jones for the sujujly of 
bacteria, and Dr. Dayton for help in the arrangement of 
instruments. 

Moreover, I take pleasure in expressing to Dr. Janewav 
and Dr. Hooker my sincere appreciation of the facilities 
afforded by them and directions as to e.xamination of blood 
]iressure, and also to Dr. Garrison in the Surgeon General's 
(.)f}ice in Washington for his kindness in translating some 
foreign journals for me. 



BIBLIOGRAPHY 

1. Blrch-Hirschfeld: Lelirbuch d. path Anat., 1882, I, 45. 

2. Bouchard and Charrin: Compt. rend. Soc. blol., 1888, III, 688. 

3. Bailey: J. E.xp. Med., 1916, XXIII, No. 6, 773. 

4. Condorelli and Mangeri: Centralbl. f. allg. Path., V. 417. 

5. Czern.v: Centralbl. t allg. Path. u. path. Anat., VII, 282. 

6. Davidson, Virchow's Arch., CL, 16; Virch. Arch., CLV, 382; 
Virch. Arch., CXCII, 226. 

7. Dantschakow: Virchow's Arch., CLXXXVII, 1. 

8. Prank: Miinch. med. Wchnschr., 1916, Nr. 13, 452. 

9. Gianturco: Giornale del la Associazone Napoletane dl medic! 
e naturalist!, 1891-2, II, 369. 

10. Hoskins-Wheelon: Amer. Journ. of Physiol., 1914, XXXIV, 
Nos. 1-2, 172. 

11. Janeway: Proc. Soc. E.xp. Biol, and Med., 1909, VI, 108. 

12. Jackson and Le Count: Tr. Chicago Path. Soc, 1914, IX, 112. 

13. Krawkow: Centralbl. f. allg. Path. u. path. Anat., 1895, VI, 
337. 

14. Lubarsch: Virchow's Arch., CL, 471. 

15. Lewis: Jour. Med. Research, 1906, XV, 449. 

16. Maximow: Virchow's Arch., CLIII. 353. 

17. Mihailowitch: Wratsch, 1896, 10S5. 

18. Markus: Tijdschr. v. veeartsenijk. Maanbl., 1904-05, XXXII, 
99. 

19. Major: Jour. Med. Research, 1917, XXXV, No. 3, 349. 

20. Nowak: Virchow's Arch., CLII, 162. 

21. Neisser-Wechsberg: Zeitschr. f. Hygiene, 1901, XXXVI, 299. 

22. Petrone: Arch, de med. experim., 1897, 1146. 

23. Pease and Pearce: Journ. infect. Dis., 1916, III, 619. 

24. Raubitschek: Verhandl. d. deutsch. path. Gesell., 1910, 273. 

25. Sczegolew: Arch. russ. de path., 1896, 409. 

26. Schepilewsky, Centralbl. f. Bacteriol.. 1899, XXV, 849. 

27. Schoukewitch: Arch. d. sc. biol., 1907, XII, 190. 

28. Stoddard-Woods: J. Med. Research, 1916, XXXIV, 343. 

29. Tarclietti: Deutsch. Arch. f. klin. Med., 1902-3, LXXV, 526. 

30. Werner: Mitteil. aus d. tierarzt. Praxis im Preuss. Staate, 
1875, 166. 

3L Zenoni: Centralbl. f. allg. Path. u. path. Anat., 1902, XIII, 334. 



ABSTRACTS OF PAPERS 



Representing Work Done in The Johns Hopkins Hospital, but 

Prepared by 

THE USE OF FREE GRAFTS OF WHOLE-THICKNESS SKIN 
FOR THE RELIEF OF CONTRACTURES' 

By JoH-X St.^ige D.wis, M, D., F. A. C. S., Baltimore, Md. 

(Abstract from Surg., Gynec. and Obst., 1917) 

■ The contractures considered are those following burns, in- 
juries and infections, in which the skin and often the subcu- 
taneous tissue has been completely destroyed. JIany methods 
have been suggested and tried for'their relief. 

The use of pedunculated flaps is especially valuable when a 
pad of fat is required in addition to the whole thickness of the 
skin, but this method can be used only in selected cases. The 
small thin grafts of Reverdin and the larger grafts of Ollier- 
Thiersch are not, as a rule, effective, especially in exposed posi- 
tions, both on account of the danger of recontraction under the 
graft and also because of the instability of the result. The 
large graft of whole thickness furnishes a .solution of the jirob- 
Wm which I have found most satisfactorv. 



' Read before the Southern Surgical Association, December, 1916. 



Published or to be Published Elsewhere than in the Bulletin, 
the Authors. 

Techxic. Preparation of the Area to Beceive the Graft. — 
All of the scar tissue should be excised, if this can be done with 
safety, but in many instances the entire part is covered with 
scar and in these only the contracture should be entirely ex- 
cised, while the movable sear tissue beyond should be utilized. 

It is of the utmost importance that the raw surface on which 
the graft is placed be perfectly dry. If the graft is placed on 
an oozing wound, the chances are that a blood clot will form 
beneath it, and this will often seriously interfere with its new 
blood supply. 

Whole-thickness grafts may also be succes.sfully placed on 
undisturbed healthy granulations wbicii are level with the skin 
edges. 

Cutting and Placing the Graft. — JIark out lightly with a 
scalpel on the skin an elongated ellipse, bearing in mind that 
the edges of the wound caused by removal of the graft should 
be appro-ximated with but little tension. Remove the skin with 
the underlying fat down to the fascia or aponeurosis covering 
the muscle. .As soon as the scalpel has penetrated the subcu- 



44 



JOHNS HOPKINS HOSPITAL BULLETIN 



[Ko. ;J24 



taneous fat the skin immediately shrinks about two-thirds of its 
original size transversely, and a little less in its length, and 
this shrinkage must be planned for. Wrap the graft in dry 
gauze until the wound from which it is taken is sutured and 
dressed. Then trim off all the fat from the graft with curved 
scissors. Perforate the graft in several places to allow the 
escape of any blood or secretions which may collect. Fit tlie 
graft into the defect, either in one piece or in several pieces, 
depending on the shape of the wound. If one piece can be 
used, it is advisable to secure it without tension by four cardinal 
sutures. In some instances a continuous horse-hair suture is 
used to fill in between the cardinal sutures, and in others a 
few interrupted sutures. Occasionally no sutures are used, as 
the graft adheres closely to the dry wound, but in these 
instances the graft should be secured by means of rubberized 
mesh. A slight even pressure should be exerted on the graft 
to hold it firmly against its base, but too much pressure should 
be avoided, as it interferes with the vitality of the graft. Tlic 
graft should be handled as little as possible. 

I consider it essential that the wound from which the graft 
is taken should be closed at once. It is better to have the graft 
too large than too small. It is desirable to fill a defect with n 
single piece of skin, as there are fewer resulting scars, but this 
is often impossible. 

Dressings. — Silver foil; dry gauze; moist salt gauze wliieh 

is kept wet, or which is allowed to dry out, are all excellent 

•dressings. Another dressing which I have found useful is a 

flexible paraffin mixture used by Carrel for another purpose. 

In children under 10 years of age, I find that it is always 
advisable to put tlic part up in a plaster cast. If tlierc are no 
contraindications I ihi not disturli this cast (or at least three 
weeks. 

Aneslkelic. — A general anesthetic is usually necessary in 
order to remove the contracture and to prepare the wound foi' 
the graft, but whole-thickness grafts may be easily secured and 
successfully transplanted with the use of a local anesthetic. 

Iso- and Zoo-Grafts. — There is much difference of opinion 
as to the advisability of utilizing iso-grafts, but I feel con- 
vinced that, when it is not possible to utilize auto-grafts, 
iso-grafts are well worth trying. 

Many successes have been reported following the use of zoo- 
grafts. My own experience is that these grafts take readily 
and receive their blood supply as promptly as ordinary grafts, 
but eventually they disappear. 

Bemarl's. — Contractures are more likely to follow in those 
cases which heal by granulation. They are much less likely to 
occur in cases where the healing is properly assisted by skin 
grafting, or by plastic o])eratioii. 

When contracture of an eyelid is dealt with, it is .seldom 
possible to remove all the scar, but all tension can be relieved. 
It is advisable to markedly over-correct in relieving these de- 
formities, as the subsequent shrinkage of the scar, and wrink- 
ling and folding of the skin in this situation have to be taken 
into consideration. 



A graft of whole thicknesss may be placed successfully in 
the midst of movable scar tissue, and accomplish its purpose. 

Gentle massage of the grafted area should be started several 
weeks after operation, and the manipulation graduallv m- 
creased until the graft moves freely with the surrounding skin. 

The operative procedure in securing thick grafts is undoubt- 
edly much greater than in securing thin grafts, and occasionally 
the after-care is difficult and tedious, but the healing following 
a successful whole-thickness graft is as stable, firm and pliable 
as the original skin. 

Contractures causing complete or partial loss of function, 
and accompanied by hideous and crippling deformities, may be 
relieved by the use of free grafts of whole-thickness skin, and 
the part restored to its former usefulness. 

A RACK FOR FACILITATING THE HANDLING OF 
SMALL DEEP SKIN GRAFTS 

By John Staige Davis, M, D., F. A. C. S., Baltimore, Md. 

(Published in the Jour. Amer. Med. Assoc, 1917) 

The appliance, is used for facilitating the handling of small 
deep skin grafts. When two or more men are working on a 
large wound, the grafts are often cut faster than they can be 
applied, and there may be no convenient way of stacking the 
artery clamps holding needles and grafts. In consequence an 
instrument is often upset or slips; the graft is brushed off, 
and is lost or else much time is wasted in trying to pick it 
up. In order to eliminate this inconvenience, I have devised 
a slotted metal rack to hold the clamps. 

The rack is made of 18-gauge sheet copper, which is bent 
so that the end view shows the form of a tra]3ezixun. The 
longest side of this figure is used as the base, and to facilitate 
clean.sing is o])en, except for three strips which are necessary 
to brace it. Tlie 12 slots are made on the side opj)Osite the 
base and each is wide enough to admit the ordinary Halsted 
artery clamp. 

The measurements of the rack are as follows : Base, 9 cm. 
long. Surface carrying slots, 6.5 cm. long. Sides, 5.5 and 
6.5 cm. long. The full length of the rack is 15 cm. 

The rack can be used with great comfort when one man is 
cutting and also placing the grafts. The 13 slots are filled 
and the rack is then moved close to the wound to be grafted, 
and all the grafts are then applied, the maneuver being repeated 
as often as necessary. It can readily be seen that an enonnous 
amoinit of labor is thus saved, since witho\it this frame each 
iiraft would have to be placed on the wound as it was cut. 

1 f more space is desired, a longer rack or two racks could be 
used. 

^\'llen a large wound is being grafted with small deep grofts. 
the method of procedure is as follows: The rack, with its 
highest side towards the operator, is placed in a convenient 
position. Then, as the grafts are cut, the clamps are droi)ped 
into the slots, and when the cutting is faster than the placing, 
the clamps are moved along progressively towards the placer, 
l,v the nurse, so lliat those grafts first cut will be apjilied first. 



Febiu-ary, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



45 



THE INTERRELATION OF THE SURVIVING HEART AND 
PANCREAS OF THE DOG IN SUGAR METABOLISM- 
SECOND PAPER 

By ADiroxT H. Clark 

(From the Department of Pathology, Johns Hopkins Hospital and 
University) 

(To appear in full in the Journal of Experimental Medicine) 

1. When a sterile, oxygenated Locke's solution, containing 
dextrose in physiological concentrations, is perfused asejotically 
tlirough the pancreas of a dog, the optical rotation of the per- 
fusate is diminished but there is no change in the reducing 
properties. An osazone with a lower melting point than glu- 
cosazone can be obtained from the perfusate. Hydrolysis of 
the perfusate tends not only to restore the original rotation but 
also yields an osazone with the same melting point as glu- 
cosazone. These changes take place also if dextrose is added to 
a pancreatic perfusate and the mixture subsequently allowed 
to incubate. An extract of a portion of tlie same pancreas 
does not bring about these changes. With a Locke's solution 
containing levulose, however, neither the optical rotation nor 
the reducing properties are altered by perfusion through the 
pancreas. A Locke's solution which contains both dextrose 
and levulose, and is therefore balanced in its rotation between 
the two sugars, when perfused through a pancreas, shows 
a displacement of the balance to the left. The reducing prop- 
erties of such a perfusate remain rmchanged and hydrolysis, 
again, increases the positive rotation. The spleen perfused 
with the same balanced solution shows neither a shift in the 
optical rotation nor a diminished reducing power. The pre- 
ceding facts can be accounted for only by a specific action of 
the pancreas on dextrose. 

2. When a living dog's heart is perfused aseptically with 
physiological concentrations of dextrose or levulose in oxy- 
genated Locke's solutions and the final perfusates hydrolized. 
there is no increase on hydrolysis in the amoimt of reduction, 
nor any significant change in the optical rotation. A similar 
negative effect is obtained when a pancreatic perfusate con- 
taining levulose is circulated through an actively l)eating heart. 
It is only when a pancreatic perfusate containing dextrose is 
fed to a heart that a perfusate is obtained, which on hydrolysis 
gives a definite increase both in reduction and in optical rota- 
tipn. The change in rotation is additional to the preliminary 
effect of the pancreas, and the increased reduction on hydrolysis 
is evidence that the change produced by a pancreas alone is 
qualitatively different from tliat produced by the combined 
action of the heart and pancreas. 

When a balanced Locke's solution of dextrose and levulose 
is perfused through a heart alone there is a definite utilization 
of sugar as shown by the diminished reduction, but the optical 
rotation is only slightly shifted, if at all, to the left. This 
shows that both sugars have been used. Hydrolysis of the 
perfusate, also, gives no material change in its reducing prop- 
erties or rotation. Such a balanced Locke's solution, however, 
tinder the combined action of the pancreas and heart, after 
correction for the preliminary change of rotation due to the 
pancreas, gives a striking and marked displacement of the rota- 



tion to the left, indicating that the selective utilization of 
dextrose has been greatly accelerated. Hydrolysis, also, gives 
a partial restoration of the original balance in rotation. 

Further evidence for the specific relation which the com- 
bined pancreas and heart have for dextrose is obtained from 
the action of bromine on Locke's solutions containing both 
dextrose and levulose, which have been perfused through the 
heart alone and through both the pancreas and the heart. If 
the dextrose is removed from the perfusate by destructive action 
of bromine, the heart taken alone is found to have used a con- 
siderable amount of levulose, whereas the heart and pancreas 
together select the dextrose, leaving the levulose fraction prac- 
tically mi touched. 

Finally, the heart, perfused with dextrose, does not lower 
the melting point of osazone obtained from the final perfusate, 
whereas an osazone from a pancreas perfusate or heart pancreas 
perfusate has a distinctly lowered melting point. After hy- 
drolysis of the perfusates, however, the melting points of the 
osazones correspond to that of glucosazone. 

The explanation wliich at present seems to be most consistent 
with these facts and with those brought out in my previous 
work would seem to be as follows: The pancreas supplies to 
a perfusate some enzyme or enzymes which have a specific 
action on dextrose as compared to levulose, changing a certain 
portion of the dextrose to a simple form of polysaccharide. 
This polysaccharide has both a lower optical rotation, and a 
lower melting point of its osazone than dextrose. I should 
regard this sugar complex as either relatively unstable, being 
hydrolized during the reduction determination, or as having 
the same reducing properties as dextrose. When, however, the 
pancreatic perfusate is circulated through a living heart tlie 
optical rotation not only continues to diminish but a new 
change occtirs. The reducing properties of the perfusate are 
now altered. Thus the effect of the heart seems to be the piro- 
duction of a change additional to that caused by the pancreas. 
The most probable explanation would seem to be a further 
polymerization of the sugar in the presence of the living heart 
to a more stable form with a diminished power of reduction. 

From the experiments here reported, it cannot be deter- 
mined whether the specific sensitization of the heart for dex- 
trose is dependent merely upon the preliminary change in the 
sugar produced by the pancreas. It seems quite probable that 
the action of the pancreatic enzyme does not cease with a 
simple polymerization but that it initiates a number of changes, 
the subsequent steps of which are dependent upon the inter- 
relation of the enzyme with the living heart. So far as the 
heart alone is concerned, there is a similarity in its action to 
that of an eviscerated diabetic animal as described by Maeleod 
and Pearce. In both there is a certain apparent utilization of 
dextrose, but for the isolated heart, at least, this utilization 
is non-specific, for it occurs almost equally well with levulose. 
In both, however, there is a certain fundamental incomplete- 
ness in the the power to utilize sugar. With the heart, by 
supplying a pancreatic perfusate, a highly specific relation is 
established between it and the circulating dextrose, which not 
only causes an immediate and rapid utilization of dextrose, but 



46 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 321 



also brings about a certain condensation of dextrose which can 
be initiated by tlie pancreas alone. 

This specific interrelation of the pancreas and heart to dex- 
trose suggests that in normal sugar metabolism this pancreatic 
enzyme, or enzymes, may be necessary; that certain -stages of 
synthesis and polymerization may he of importance as inter- 
mediate steps in carbohydrate utilization : and that when there 
is an insufTiciency of tlie pancreatic function, though the body 
tissues are supplied with an abundance of dextrose which can 
1)0 burned to a certain extent, yet the essential steps, by which 
dextrose is pr('])nr('il for nnrninl utiliziitioii, cannot take place. 

A NEW METHOD FOR MAKING WASSERMANN 
ANTIGENS FROM NORMAL HEART TISSUE 

By Ct.ahexce A. Neymax.n and Leslie T. Gagkii 
(Abstract from Journal of Immunology, October, 1917) 

After describing the methods in use for tlie production and 
tibration of Wassermann antigens, and giving an account of 
tlieir investigations of the various lijwids of beef's heart which 
were pi-e]iarc<l according to Ei'lantlsen's mctliod, the authors 
say : 

"The dianiiiionionophosphatidcs which comprise over half 
by weiglit of the .secondary alcohol soluble lipoids, have an 
extremely high antigenic value as well as a low anticomplemen- 
tary and hemolytic titrc. Therefore it is with this group that 
we are primarily concerned in making a good Wassennaiui 
antigen. 

"Considering these I'acts and using the knowledge gained 
we propose the following methods for making antigens: 

" Take a normal beef heart and remove all the endo- and 
pericardium, larger blood vessels and fat. Grind the heart 
muscle very fine and spread it in a thin layer on glass plates. 
Dry by means of an electric fan for 21 hours, turning the layer 
of tissue after 12 hours. A parcbnunit-like dry sheet of tissue 
results. Break this up and grind it again, thus producing a 
line dry powder. I'lit this in bags and dry in an incubator 
at 37° C. for scvei-al days. Extract with ether in a Sohxlet 
apparatus for 12 hours, or in an ordinai-y wide-mouthed bottle 
at room temperature live or six times until the supernatiint 
ether is no longer colored yellow. The l.itter procedure takes 
from 8 to 10 days. The ether should cover the muscle pow-der 
to a dei)th of I'lum 3 to 3 inches. Dry the j)owder by 
spreading it out on a sheet of paper for .several hours. Now 
extract the powder with absolute or Do per cent alcohol for 10 
days. The alcohol should cover the ])owder to a depth of half 
an inch and it will gradually assume a light yellow color. 
Titrate the antigen thus obtained. Extract the powder a 
second time with alcohol for 11 days. Titrate this antigen. 

" Both extracts will. prove to be good plain extracts. Some- 
times the second will be better than the first, for the dianii- 
nomonoi)hosphatides .seem to go into solution after sonu^ of the 
other groups of the secondary alcohol extract have been dis- 
solved out. 

" In order to ])roduce an acetone insoluble extract the ])lain 
extracts are united, evaporated to dryness at room temperature 
liv means of a fan and treated with an excess of ether, 'i'lie 



ether-soluble portion is filtered off, allowed to evaporate, treated 
with an excess of acetone and the sticky brown residue is 
finally dissolved in a minimum quantity of absolute alcohol. 
The solution is then filtered and again titrated. 

" This preparation consists almost entirely of diaminomono- 
phosphatides and with 10 hearts prepared in succession has, 
each time given an antigen which bound at least 1 to 1600, 
and showed a low anticomplementary litre and no hemolytic 
properties. 

" A cholesternized antigen can be made by adding 0.2 gm. 
of cholesterin to 100 c. c. of the plain extract or of the acetone- 
insoluble preparation. The cholesterin will dissolve very 
readily in either of those phosphatide solutions, much more 
readily than in the same amount of absolute alcohol. After 
the addition of cholesterin the antigen is again titrated. 

" These antigens have been in use in our laboratory for the 
past six months. They have proven reliable in every way and 
have solved the problem of finding a certain and definite method 
of obtaining a reliable, fairly equal, and powerful product. 
Though these antigens pick up weaker positives than our 
former pre])arations t1u>y have never given false jiosjtjves."' 

A NEW PATHOGENIC SPOROTRICHUM. FOUND IN A CASE 

OF ACUTE ARTHRITIS OF THE KNEE, FOLLOWING 

INJURY 

By S. B. WoLMAcn, M. D., W. R. Sissox, M, D., and 
F. C, Meiek, Ph. D, 

{From the Department of Pediatrics. The Johns Hopkins 
Hospital) 

Instances of infection with sporotricha following injury, 
in America, are of unusual interest in the consideration of 
presumably free living pathogenic fungi. The study of the 
culture from the case here jiresented has revealed a new variety 
of sporotrichum for which the name Sporotriclium couneil- 
manii is proposed. 

The culture of this oiganism was obtained from the knee- 
joint of a boy of 10 years. This patient received a puncture 
wound of the right knee from the nail of an ash barrel. Fol- 
. lowing the injury there took place within 12 days, signs and 
symptoms of an acute arthritis wliieh could not be explained 
by the common causes of this condition. The swollen knee 
was aspirated repeatedly. Large quantities of sanguineous 
muco-purulent material were recovered. This showed micro- 
scopically numerous jjus cells without the presence of demon- 
strable organisms. Cultures showed the presence of a fungus 
growth. Using a suspension of this fungus as an antigen, the 
patient's serum showed complete fixation in various dilutions. 
Similarly, agglutination tests with the patient's serum were 
positive up to dilutions of 1-100, The jjationt was observed 
at the hospital for six months. The condition of the knee was 
unimproved after the usual forms of treatment. X-ray exami- 
nation showed no bony changes. Complete fixation of the joint 
took place. Shortly before his discharge from the hospital all 
signs of acute infection di.'tappeared. A study of the patho- 
genicity of the fungus isolated from the patient's joint was 
made by injecting guinea-pigs and rabbits iiitraiieritoiioally, 



FiciiULAiiV, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



47 



hy injecting rats intravenously and rabbits intraarticularly. 
By the first method the organism was found to be of low patho- 
ucnicitv. causing a granulomatous lesion of the peritoneal 
Ivmph nodes. These animals did not succumb to the injection. 
Tlie intravenously injected rats showed multiple focal abscesses 
iu the brain, thoracic and abdominal organs. After the injec- 
tion of the fungus into the knee-joint of the rabbit, an acute 
arthritis was produced wiiich simulated in every way tliat of 
llie ])atient. 

ilicroscopically. tlie lesions resembled those of actinomycosis 
;iud the organisins of cutaneous blastomycosis and coccidioidal 
granuloma. The first reaction is the collection of polymorpho- 
nuclear leucocytes and endothelial cells about the organisms, 
(iiant-cell formation and the taking up of the spores by endo- 
thelial cells and giant cells occur. The mycelial fragments 
always seem to disappear soon after injection. At the periph- 
ery of the lesions fibroidblast proliferation becomes active. 
The lesion progresses only following the germination of t\\e 
spores with the production of branching filaments radially 
arranged. Late lesions consist of fibrous nodules containing 
foci of soft yellow necrotic material. The organism was early 
identified as a sporotrichum. It grows readily on all ordinary 



culture media at room temperature. The gross cultural appear- 
ance differs from most pathogenic sporotricha in that it 
produces a profuse areal growth of white cotton-like hypha\ 
This has not been seen with the other sporotricha. iiicro- 
seopically the hypha^ and spores are distinctly larger than tiiose 
of other sporotricha. Furthermore, this organism does not 
produce lateral spores or conidia from vegetative hyphre. liike 
other sporotricha there is great variation both in regard to the 
form of the growth and pigment production. Comparison oi" 
this organism with Sporotrichum schenkii and Sporotrichum 
beurmannii ; and with cultures from a case of sporotrichosis 
described by Page, Frothinghani and Paige, shows striking 
differences, especially the gross cultural appearances. Compari- 
son also with descriptions of other isolated pathogenic sporo- 
tricha warrants us in considering this an hitherto undescribed 
form. It resembles most closely Sporotrichum jeanselmei in 
gross cultural characteristics, in pleomorphism and in luxur- 
iance of growtli ufjon simple media. It shows, however, a much 
greater tendency to areal growth of the filaments. Micro- 
scopically, it is different from all species in the absence of 
lateral clusters (jf sjjores. The form of the organism in lesions, 
namely, tliat of branching liyi)ha% is unusual. 



TITLES OF PAPERS APPEARING DURING THE YEAR, ELSEWHERE 
THAN IN THE BULLETIN, BY PRESENT AND FORMER MEM- 
BERS OF THE HOSPITAL AND MEDICAL SCHOOL STAFF 



."■.U7-r)lT 



Abel, J. J., and PiNCOFrs, M. C. 

Un tno prosence of albumoses in extracts of tho post 
hypophysis cerebri. — Proc. Nat. Acad. Sc, Balto., inn 

ABEL, J. J., PiNcoFFs, M. C, and Roi'iller, C. A. 

1)11 the presence of albumoses In the tissues and in the hlooil. wl 
special reference to their occurrence in the gastrointestinal mucoi 
— Im. ./. Physiol, Balto.. 1917, xliv, 320-343. 

At ER, J., and Gates, F. L. 

Kxperiments ou the causation and amelioration of ailii'iialiii puliiiouii 
edema. — .7. Ea-prr. II., Balto., 1017. xxvi, 201--.»i;(i. 

AuER, J., and Klei.xer, I. S. 

The effect of coagulation of the pancreas in situ.- 

Biol. <C- Mc<l.. N. v., 1!>17, xiv. iril-1.52. 

Morphin hyperglycemia as a test for pancreatic 



Kxi>er. 
-Ibid.. 



AuER, J., and Meltzer, S. J. 

Prolonged constriction of the bloodvessels by snbiutnneoiis injection of 
adrenalin into the e.ar of a rMbbit. A demonstratinn. |.\bstr.l — I'ror 
Soc. liJ^iicr. Iliol. d- J/rrf., X. Y.. inifi. xiv, .">4. 

BAfeusY, c., Jr. 

Braiij surgery. — Siiri/.. diiiicr. d- (Hi.it.. Chicago, 1017, xxv. 7l'.'-7l'7. 

Barker, L. f. 

The iinportii,,,.,. .d' a knowledge of syphilis, and cspcciallv of visc-ral 
?-*'j^|;'J',-5,°'" Scneral medical diagnosis.— .li«, J. Hyph., St. Louis, 1017, 

The stiid.v of the.internal secretions: an introduction. — EndociiHologii, 
I.os Angeles, Cal,, mi 7 , 1.4 



Typb 
101 



with Cum plications : intestinal hemorrhages, otitis media, 
. ilecuhitus, peripheral neuritis, — luteruut. Clin., Phila., 



v' "l'"i'"'''rhi'l''i "JV^"""!" t*'."'"^''- I'rohil'l.v meningococcal.— .l/c(f. Clin. 



flbrillat 
gressivc 
the Aim 



(central 
[III 



scs ot fibrillation of muscular tissue, C 
(ral stenosis and mitral insumciencv. ( 
lar atrophy (Vulpian-Bernhardt 



lienne lypel. — Ihid'. 73-100 
The wid..,- Held of work of the National Com 
Hygiene.- l/.ii/. //,/,(/., Cimcord. N, II„ 1917 j 4.(1 
Cerehrospinal rever, choh.ra Asiatica. plague,' >),.■ i 



(Mnsser & Kelly 



The 



iitic.-iti. 



1017, Iv, 206-2n.S. 
and relations of 
ligharn. Ala., 1017, 



.S'o»»i. .U. ,/.. , 
On the growth 

Uifantile paralysis, ainte anteri( 
<Hsease, t.Vbstr.l — Ihid.. 130, 
Bakkkr, l. p., and Bridgviax, E 
Kxtreme prolongation of condiu-i 
example resulting from digilalis 
I'll I, Ixviii, 003-007, 



cardio-vi 
?. 22-29, 
'oncerniii 



ie I, Atrial 
se IT. Pro- 
bvariety of 

r.)r Menial 

treatment. 

disease. — 

•■ known ■•« 
[eine Medin 



Barkkii, L. F., and Moskm-iiai., H. 0, 

I 111 i he control of the s.^'niptoms of diabetes insipidus by subcutaneous 
iii.i'i linns of extracts of the hypophysis cerebri (pars posterior and pars 
iiiteriiiedial,— .l»i, ./, VkjI.. Bait., 1017, i, 440-467. 

Barker, L, F., and Spri-xt, T. P. 

The treatment of some cases of so-called •' 
regimen thai has been found helpful. — ./. .4hi 
Ixix, 1010-1027. 

Batchelor, M. D,, Ford, W, W., and Blackfax, K. D. 

Some (diservations on intestinal bacteria in children. — .Iwi. ./, Itis. 
Child., Chic.igo, 1017, xiv, 3,"i4-:Ui4. 

Bayxe-Joxes, S. 

The blood-vessels of the heart valves. — .\m. .1. .inol.. Phibl.. 1017, xxi, 

440-4(1,-!. 

■rypli.dil meningitis : with icpi>rt of a case, — -liii. .7. Jf. Sc, Phila,. 1017, 

cliv. .-.,-|-{i3. 

Equilibria in precipitin reactions. The coexistence of a single frei' 

antigen and its antibody in the same serum. — /. Exper. M.. Ball.. 1017. 

xxv. 837-8.">3 : also Stud. Itockejeller Inst. M. Research. N, Y., 1017, 

xxvii, 239-2.i.'5. 



Bayxe-Jones, S 
The reaction 
hvdr<>«en-ion 
.1; 



Feltox, L. D., and Hrs.SEY, R. G, 
eaction of the cerebrcis]>inal tluid. Preliminary report on 
:en-i(in concentration as .li't.-i-mini'd bv the coloriinetrlc method, — 
Int. llid.. fhlcago, 1017, xix, 10S.--100G, 



Bayne-Joxes, S., W.\ters, C. A,, and Row.xtree, L. G, 

Boentgeuography of the lungs. Uoent.genographic studii 
animals after intratracheal injection of iodoform ei 
3Ied.. Chicago. 1017, xix, ,-i::.s-,->40, 

Beall, F, C, 

The treatment of retroversion of the uterus,- 
Worth, 1017. xii, 428-30, 

Berxheim, B, M, 

The limits of bleeding cons 
■/, .U. .Sc, Phila,, 1017, cliii, .-)7,-|-,-.i 
Sodium citrate blood transfusion 
Chicago, 1017, Ixix, 3,->0-3i;3. 

Blackfax, K, D, 

Ijead poisoning in <diildr 



-Ti-j-as .State .1. 1/,, 



lered from Ihe clinical standpoint, — .1 in, 
•)7,-|-,-.S3. 

onip.irison, — .7, Am. U, Ass., 



of . 



vuls 



;. — .Im. •/. .17, 



vilh 



Blackfax, K. D.. and Daxdv, W. E. 
Internal hydrocephalus. Second paper.- 
1017. xiv, 424-443, 

Blackfax, K. D., Ford, W. W,, and Batchelor, M, D. 

Some observations on intestinal bacteria in children 
Child.. Chicago, 1017. xiv, 3,-.4-3fi4. 



/. nis. Child.. Chicago, 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 324 



Blanton, S. 

Unusual case of speech inhibition. — J. A\>norm. Psychol., Bost., 1U17, 
xi. 325-327. 

Retarded school children in Madison, Wisconsin. — Psychol. Clin., 
Phila., Pa., 1917, x, 250-203. 

Bloodgood, J. C. 

Diagnosis of cancer. — Boston M. <£ S. J., 1917, cixxvi. 317. 
C'iincer and the oral cavit.v. — Dental Reg., Cincin., 1917, Ixsi. 224-228. 
The pre-existing lesions in the oral cavity and their relation to malig- 
nant diseases — Dental Jiev., Chicago. 1917, xxsi, 357-378. 
Letter to the medical profession. — Illinois M. J., Chicago, 1917, xxxii, 
291-292. 

The Carrel-Dakin treatment. A replv to Dr. Bevan. (Letter.) — J. Am. 
M. Ass., Chicago, 1917, Ixix, 2061-2062. 

The prevention of cancer. — Maryland M. J., Bait., 1917, Ix, 68-70. 
The duty of the medical man in the present crisis. — Ibid., 164-166. 
National standards for first aid. — Penn. M. J., Athens, 1917, xx, 
060-670. 

Medical preparedness in the great drive for democracy. — South. M. J., 
Birmingham Ala., 1017, x, 746-752; also ./. Florida M. Ass., Jackson- 
ville, 1917, iv, 63-69. 

The breast; lesions of the female breast. In: A treatise on regional 
surgery. (Binnie.) Phila., 1917, i, 557-630. 

Surgical treatment of diseases of the thvroid gland. In: Practical 
treatment. (Musser &. Kelly, i 1917, iv, 470-475. 

Bl.UMER, G. 

Food intoxication and poisnninir bv reptiles and insects. In: Practical 

trentinent. (Musser & Kellv.) 1917, iv. 157-162. Rat-bite fever. 

lljifl.. :!44. 

.\ discussion of the deleti-rious effects of competitive athletics. — .llban}/ 

•if. Ann., 1917, xxxviii, 151-163. 

Report of a case of paramyoclonus multiplex (myokimia). — I'roc. 

Connect. M. Soc, New Haven, 1917, cxxv, 171-176. 

Bra.ncii, J. R. B. 

A day in the hospital. — Yale AUimni WeckUi. Suppl,, 1917. xxvi. 4. 

Bridgman, E. W., and Barkicr, L. F. 

Extreme prolongation of conduction time in the bundle of His. An 
example resulting from digitalis therapy. — •/. Am. M. Ass., Chicago, 
1917, IxviU, 903-907. 

Brook.s, B. 

Studies in regeneration and growth of Imne. The demonstration of new 
foniied bone by intravital staining. — Ann. Surg., Phila.. 1917, Ixv, 

Studies in bone regeneration ; an experimental study of bone trans- 
plantation by means of a vital stain. — Ibid.. Ixvi. 625-639. 

Brown, Hklen W. S. 

Thi' deforming influences of the home. 

1917. xii. 49. 

A liliTary forerunner of Freud. — Psi)choanalut. Re 

& X. Y.. 3 917, iv, 64-69. 

Brown, N. W. 

ysmal tacbycard 



.ibiiorm. Psychol., Bost., 
I^ncaster, Pa., 



1917, xiv, 287-29, 
Brown, T. R. 

The rebitionship lietwei-n d 



(■liiidh I.— .41 



I of 



1 general diseases.— 
.». Mt, iirnT \ <■■« . lliiulington. Ind.. 1!)17 iv Si',6-.S77 
^."""' "'-I'" ird. -.11,1 ii..t(.s. The cause .,( tlir symptoms of gastropto- 

^'^ II" iL i.iii ,in. , ,,i ,.| iMingenitally liii;li il lenum and of duodenal 

'"■ I'V'M. ...'.I.. ,,,h . :iihI 111.' vaiiie i.f i).vl(.n.]iliisty in the treatment of 
Miili jN.N. i;,,;, ( tui. .V. .4»i., Plilla., 1917. i. 185.189. 
Visceroptosis and chronic appendicitis. — Ibid.. 1.89-191. 
The medical after-care of surgical patients after abnormal operations. — 
Ibid., ini-193. 

Bunting, C. H., and Yate.8, J. L. 

Rysnlts of treatment in Ilodgkln's disease.-^A Am. .1/ t.<i.9 Chica'o 
191 1, Ixvlil, 747 751. „ , 

Bt'RKKT, W. C. 

1 1 III 



Changes In the iieriphe 
splenic blood Into the ; 
xxvl, S49-.Sfi5. 



ral lin-ul.ilion.^^/. Expc 



If.. Bait.. I9I7, 



BURNAM, C. F. 

New growths of Ih 
ment with radium.- 



niedlastinum with special refcTence to thr^ir 
-J. Am. M. Ass., Chicago, 1917, Ixlx, 989-996. 



.T. E. 

bbnlder i hanges due to lesions of the central nervous .sy.stem ■ 
, .^... , -Surg., aynec. li Obst.. Chicago,' 



id treatm 
ilinn 



hii 



nns on the use of thorium in pyelograpbv. — ,/. 4m If 
' 111, i. ■. 1917, Ixvlil, 5,-J3-r)36 : also r.\bstr.l South. ,U. ,/.. Blrmir"- 
.M.'i.. 1917. X. 432. " 

Burns, J. E., Burrows, M. T., and Suzuki, V. 

Studies on the growth of cells. The eultlvalinn of bladder and prostatic 
tumors outside the body.—,/. Irol.. Bait., 1917. 1. 3 15. 

Burrows, M. T. 

The oxygen pressure necessary tor cellular aetlvilv. — li 
I'."-i I'li; IT. xlll, 614-615. 

I'ssure necessary for tissue activity. — lii 



. .1. Phiisiol., 
■I. I'hiisinL, 
1916 17, xl, 
-/!»'<f., 1917. xil. ini 166. 
Burrows, M. T., Burns, .1. E., and Suzuki, Y. 

Studies on the growth of cells. The cultivation of blailder and prostatic 
tumors outside the body. — ,/. Vrol., Bait., 1917. 1, 3 15. 



!■■ ill , ii'i 7 \iiii. 13-; 

•rVr"'>-o ' "" "'8"'"""^ srowth. — .diiat. Record, Pbila., 

The signlflcance of the lunula of the nail.- 



BuRBows, M. T., and Netmann, C. A. 

Studies on the metabolism of cells in vitro. 
a-amlno acids for embryonic chicken cells. — , 
1917, XXV, 93-108. 

Burrows, M. T., and Park, E. A. 

The study of a small outbreak of poliomyelitis in an apartment house 
occurring in the course of an epidemic in a large city. — Arch. Int. Uph ' 
Chicago, 1917, xx, 56-78. -"f . 

Camac, C. N. B., and Pool, E. H. 

Pericardiotomy for suppurative pericarditis following pneumonia. — 
Am. J. M. Sc, Phila.. 1917, clui, 509-528. 

Campbeli,, C. M. 

The subnormal child ; a survey of the school population in the Locust 
Point district of Baltimore. — ilent. Hyg., Concord, N. H.. 1917, i. 

Educational methods and the fundamental causes of dependency. — 

The mental health of the community and the work of the psychiatric 
dispensary. — Ibid., 572-584. 

Caulk, J. R. 

Preliminary renal drainage with special reference to the two-stage 
operation on the kidney. — Ann. Surg., Phila., 1917. ixv, 593-596 
Etiology of renal infections. [Abstr.] — Interstate it. J., Chicago. 1917. 
xxiv, 228-232. 

Sterility in the male. [Abstr.] — Interstate M. J., St. Louis, 1917, xxiv, 
541-544. 

Ureter catheter drainage In the treatment of renal infections, with 
special reference to the infected hydronephrosis complicating preg- 
nancy. — J. Am. M. Ass., Chicago. 1917, Ixvili, 675-677 ; also l-^bstr.l 
South. M. J., Birmingham, Ala., 1917, x. 673-674. 

Caulk, J. R. and Barnes, F. M., Jr. 

Cystoscoplc examination of the bladder in psvehoses. — •/. Mi.isouri u. 
Ass., St. Louis, 1917. xiv, 329-332. 

Caulk, J. R., and Geeditzer, H. G. 

Observations on the bladder in diseases of the central nervous system. 
An analytical study of 117 cases. — .4ik. ./. Syph.. St. Louis. 1917, i. 
42-57. 

Cecil, A. B. 

Surgical treatment of seminal vesiculitis. — CaliJ. State J. M.. 
San Fran., 1917, xv. 497-500. 

Reflex retention of urine. — J. Am. M. Ass., Chicago, 1917. Ixviil, 44ii 
443 ; also [Abstr.] South. U. J., Birmingham, Ala., 1917. x, 441. 

Cecil, H. L. 

The use of kephalln to hasten coagulation and hemostasis after surgical 
operations. — •/. Am. M. .\ss., Chicago, 1917, Ixviil, 628-629. 

Chesney, A. M. 

Treatment of pneumonia by ethylbydrocuprein. — Med. Rcc, N. Y. 

1917, xci. 86-87. 

Treatment of pneumonia by optochln. — Xew York M. .1. [etc.], 1917. 

cv, 235. 

The latest period in the growth of !>acteria. — Stud. Rockefeller /».<^ 

M. Research, N. Y., 1917. xxvi. 503-534. 

Chesney, A. M., and Amoss, H. L. 

a report on the serum treatment of twenty-six cases of epidemic polio- 
myelitis. — J. E.ri>er. M.. Bait., 1917, xxv, 581-608; also Stud. Rocke- 
feller Inst. M. Research, N. Y.. 1917. xxvll, 125-152. 

Chesney, A. M., and Moore, H. F. 

A study of ethvlhvdrocuprein (optochln) In the treatment of acute 
lobar pneumonia. — Arch. Int. Med., Chicago, 1917, xix, 611-682. 

Churchman, J. W. 

in modern warfare.— ilo.sfoa M. .t .8. ./.. 1917. 
-116. 

Clark, A. H. 

The interrelation of the surviving heart and pancreas nf the dog in 
sugar metabolism.-^/. Rr/jcr. ,1/.. Bait.. 1917, xxvl. 721-744. 

Clark, J. G. 

New surgical problems due to the war. — Surg., Gynec. d Obst.. Chicago, 

1917, xxv. 700. 

Radium therapy in uterine hemorrhage of benign origin.— Tr. Am, 

Gunec. Snc. 1917. xlll. 

The surgical treatment of Intestinal stasis. — In: Practical treatment. 

(Musser & Kelly.) 1917, Iv, 665-660. 

Ci^rk, J. G., and Block, F. B. 

Ultimate results following nephropexy in cases of symptomatic nephro- 
ptosis. — .4)111.. Surg., Phila.. 1917, Ixvl, 479-487. 

Clark, J. G., and Noimis, C. C. 

Results following treatment of pelvic Inflammatory lesions by surgical 
measures.— SiD-i;., aynec. rf Obst., Chicago, 1917, xxv, 33-39. 

CLAU.SEN, S. W., Hhj.er, At.ma, and Mosbnthal, H. 0. 

The non-protein nitrogenous constMuents of normal human muscle. — 
Proc. Soc. Erper. Itiol. if Med., N. Y., 1!>17, xiv. 170 171. 

Clouoh, Mildred C. 

The cultivation of tubercle bacilli from the circulating blood in miliary 
tuberculosis. — Am. Rev. Tuberc, Bait., 1917, i, 598-621. 

Conn, S., Bailey, A. A., and Holtz, P. R. 

On the genesis and Inhibition of extensor rigidity. — -4m. .J. Physiol., 
Bait, 1917, xllv, 239-258. 

Cole, R. I. 

Suggestions concerning the prevention and cure of acute lob.nr pneu- 
monia. — .4?n. J. Pub. Health, Concord. N. II.. 1917, n. 
Report of studies concerning acute lobar pneumonla.- 
Chlcago, 1917. Ixlx, ,505-508. 



Febkuaey, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



49 



1917 
-Pfiin. J/. J., Athens 



Ea-pei: 3/., Bait.. IDIV 



J. Dis. Child.. Chicaj 



The neutralization of antipneumococcus immune bodies by Infected exu- 
dates and sera. — J. Exper. M., Bait, 1917, xxvi, 453-475. 
The treatment of lobar pneumonia. The importance of determining the 
etiologic agent in each case of pneumonia and full discussion of the 
various methods of treatment ; the use of digitalis in the earl.v stages.— 
Med. Clin. N. Am., Phila., 1917. i. 545-561. 

The nature of pneumonia and the senmi treatment. — -\ew 1 orA- .1/. ./. 
[etc.]. 1917, cv, 233-234. 

Present status of serum therapy. — yew Tork State M. ./., 
xvii, 347-357. 

The specific treatment of acute lobar pneumonia. - 
1916-17, XX, 345-351. 

Cole, R. I., Avert, O. T., Chickerikg, H. T., and Dochbz, A. R. 
Acute lobar pneumonia, prevention and serum treatment. — ilonogr. 
Rockefeller Inst. M. Research, N. Y., 1917, No. 7. 

Cole, R. I., and Chickering, H. T. 

Typhoid fever. — In: Practical treatment. (Musser & Kelly, i 1917. 
iv", 183-211. 

Cole, R. I., and Moore, H. F. 

The production of antipneumococcic serum. - 
xxvi, 537-561. 

CoL.STON, J. A. C, and Young, H. H. 

Injuries to the pancreas following operations on the right kidney. — 
J. Urol., Bait., 1917, i, 179-191. 

Conrad, H. B. 

A case of pneumonia of unusually short duration. — Am. .J. Dis. Child., 
Chicago, 1917, xiv, 296-300. 

CULLEN, T. S. 

The surgical methods of dealing with pelvic infectious. — Surg., aynec. i£ 

Obst., Chicago. 1917, xxv. 134-146. 

America's place in the surgery of the world. — Ibid., 376-390. 

CUSHING, H. 

Tumors of the nervus acusticus and the syndrome of the cerebello- 
pontile angle. — Phila. & Lond., 1917, W. B. Saunders Co.. 296 p., S = . 
Anosmia and sellar distension as misleading signs in the localization 
of a cerebral tumor. — J. Nerv. & Ment. Dis., N. T.. 1917. xliv, 415-423. 

Dandy, W. E., and Blackfan, K. D. 
Internal hydrocephalus. Second paper.- 
1917, xiv, 424-443. 

Davis, D. M. 

The effect of dextrose given intravenously on blood composition and 

urinary secretion. — Am. J. Physiol., Bait., 1917. xliii, 514-529. 

The effect of calcium, water and other substances given intravenously 

on blood composition and urine secretion. — /. Urol., Bait.. 1917, i. 

113-134. 

Davis, D. M., and Gorton, W. S. 

A modified Woodyatt pump. — J. Urol, Bait., 1917, i, 135-138. 

Davis, D. M., and Rosen, R. 

Surface sterilization of tissues for bacterial studies. — J. Infect. Dis., 
Chicago, 1917, xxi, 327-337. 

Davis, D. M., and Stone, H. B. 

Studies on the development of toxicitv in intestinal secretion. — •/. 
Exper. M., Bait., 1917, xxvi, 687-691. 

Davis, E. G., and Young, H. H. 

Double ureter and kidney, with calculous pyonephrosis of one half : 
cure by resection. The embryology and surgery of double ureter and 
kidney. — J. Urol. Bait., 1917, i, 17-32. 

Davis, J. S. 

A comparison of the permanence of free transplants of bone and car- 
tilage. — Ann. Surg., Phila., 1917, Ixv, 170-174. 
Some of the problems of plastic surgery. — Hid., Ixvi. 88-94. 
A rack for facilitating the handling of small deep skin grafts. — J. Am. 
M. Ass., Chicago, 1917. Ixix. 997-998. 

The use of relaxation incisions in dealing with extensive unstable 
hears. — lUd., 2085-2986. 

The use of free grafts of whole thickness skin for the relief of con- 
tractures. — Surg., Gvneo. £ Ohst., Chicago. 1917, x.w, 1-8. 
The pathology of the major vestibular ducts and glands. — 7"r. .Im. .Iss. 
Obst. a aynec, 1916. York. 1917, xxix. 177-206. 

Dick, Gladys R., and Dick, G. F. 

The bacteriology of the urine in focal infections: its relation to 
nephritis. — Arch. Int. Med., Chicago, 1917. xlx, 493-498. 

Dickson, E. C. 

Botulism ; the danger of poisoning from vegetables canned hv the cold- 
packed method. — J. Am. U. Ass., Chicago, 1917, Ixix, 966-968. 

Dunton, W. R., Jr. 

The^ exammajion ^o^f_ paUents suspected of being insane.— i/ed. Rec., 

History of Occupational therapy Occupation for patients advocated by 
Benjamin Rush in the eighteenth centurv — many in earlv times recog- 
ni^zed the therapeutic jalue of work— early work'of Bethlehem Hospital 
jjj.^ country. — Mod. llosp., St. Louis, 



Emmons, A. B., 2d. 

K y!*19!-7. ti^"%isll^ "■""' " '""' '" "^^ ^"'"■■'^•- 

4ni°in?' ™'''® — "" opportunity for the medical profession. — Ibid., Ixxvi. 



-.4 m. 



Obst., 



401-405. 

The young doctor and health Insurance. 

Chicago, 1917, Ixviii, 651-652. 



EELANGEK, J. 

The movements of the artery within the compression chamber during 

indirect estimations of the blood pressure. — Am. J Physiol Bost 

1916-17. xlii, 588-589. 

Further observations on the mechanism of the arterial compression 

sounds of Kcir.itli.ifr : the preanaerotic phenomenon. — -J. Missouri M. 

A.ts., St. Louis. i:i|T. xiv. 258.- 

The rrde of lin h '-i l:i\v in clinical sphygmomanometrv. A reply to 

A. M. Bleile. — N( i. »,c. Lancaster, Pa., 1917, xiv, 3S4-3S5. 

Erlanger, J., Gesell, R., Gasseb, H. S., and Elliott, B. L. 

An experimental study of surgical shock. Preliininarv report. — •/. Am. 
M. Ass., aiicago, 1917, Ixix, 2089-2092. 

Erlanger, J. and Woodyatt, R. T. 

Intravenous glucose injections in shock. — J. 
1917. ixix, 1410-1414. 



.If. .iss., Chicago, 



-Tr. New Tork Path. Soc, 1916-17. 



-Anat. Record, Phila., 



Evans, F. A. 

Gaucher splenomegaly in a child.- 
xvi, 114-124. 

Evans, H. M., and Baetelmez, G. W. 

A human embryo of seven to eight somites. - 
1916-17, xi, 355. 

Felton, L. D., Hussey, R. G., and Bayne-Jones, S. 

The reaction of the cerebrospinal fluid. Preliminary report on 
hydrogen-Ion concentration as determined by the colorimetric method. — 
Arch. Int. Med., Chicago, 1917, xix, 1085-1086. 

Felton, L. D., and Maxcy, K. F. 

The colloidal gold reaction of the cerebrospinal fluid in acute polio- 
myelitis. — J. Am. M. Ass., Chicago, 1917, Ixviii. 752-754. 

Finney, J. M. T. 

The diagnosis and choice of operation in certain affections of the 
stomach and duodenum. — Hew York State J. M., N. T., 1917, xvii, 
203-210. 

Finney, J. M. T., and Friedenwald, J. 

Gastric polyosis. — Am. J. M. Sc., Phila. & N. Y., 1917, cliv, 683-689. 

Finney, J. M. T., and Walker, G. 

Abrogate the patent on salvarsan. (Letter.) — J. Am. M. Ass., Chicago, 
1917, Ixviii, 1572-1573. 

Fishbaugh, E. C. 

Spontaneous anastomosis between transverse colon and duodenum. — 
J. Am. M. Ass., Chicago, 1917, Ixviii, 624-627. 

Fisher, A. L. 

Syphilitic bone and joint lesions simulating tuberculosis. — J. .im. M. 
Ass., Chicago, 1917, Ixviii, 366-367. 

Flexner, S. 

Epidemic poliomyelitis: its nature and mode of infection. — Am. J. M. 
Sc, Phila.. 1917. cliii. 157-160. 

Mode of infection, means of prevention and specific treatment of 
epidemic mrnin-ii is. — J. Am. M. Ass., Chicago, 1917, Ixix, 639-645; 



721-' 



If infaiiiili |i:ii:il\sis comes this summer. — Med. Insur. d Health Con- 

serv., Liallas. i:ilT, xxvi. 244-347. 

Mechanisms that defend the body from poliomyelitic infection, (a) 

external or extra-nervous, (b) internal or nervous. — Proc Xat. Acad. 

Sc, Bait.. 1917. iii. 416-418. 

Recent advances in knowledge of poliomyelitis. Address before N. Y. 

Committee on After Care of Infantile Paralysis Cases. New York 

Academy of Medicine. May, 1917. (Published by X. Y. Committee on 

After Care of Infantile Paralysis Cases.) 

Flexner, S., and Ajioss, H. L. 

The passage of neutralizing substances from the blood into the cerebro- 
spinal fluid in poliomyelitis. — J. Exper. M., Bait., 1917. xxv. 499-505 : 
also Stud. Rorkrfrllrr In.it. M. Research, N. Y.. 1917, xxvii. 43-49. 
The relalinn of tlu' iiM'iiiiiL:es and choroid plexus to poliomyelitic infec- 
tion.— 7()/rf.. .-2.-. -.:;7 : a Is., .((fd., 69-81. , ,^.^ 
Survival of the |i..liniiiv..litic virus for six years in glycerol. — Ibid., 
539-543 : also ibid., s:'.-sl . 

Flint, J. M. 

The healing of gastro-i 

Ixv. 202-221. ^ . ... 

A combined method tor the localization and extraction of proiectiles. — 

Mil Surg., Wash.. 1917, xl, 259-273. 

Ford, W. W., Blackfan, K. D., and Batchelor, M. D. 

Some observations on intestinal bacteria in children. — .4m. .7. Dis. 
Child., Chicago, 1917. xiv, 354-364. 

Fbontz, W. a., and Young, H. H. 

I'reliminarv treatment for prostatectomy in unfavorable cases. — J. Am, 
M iss. ('hicago. 1917. Ixviii. 526-530; also [Abstr.] .South, if. J.. 
Birmingham. Ala.. 1917, x. 431-432. 

FUTCHER, T. B. 

Acromegaly. — Med. Clin. -Y. Am. Phila.. 1917, i. 131-143 



iitestinal anastomoses. — .inn. Surg., Phila., 1917 



In: Practical treatment. 
-Ibid., 510-512. 



(Mus 



leroderma, Raynaud's disease, and chronic arthritls.- 

Ihid.. 14.^.-1. -.4. 

riiali.'tis insipidus. — 

1917. iv. .-.IIS r,09. 

Arthritis il.'fonnans.- 

Gout— /((id., 513-515. 

Lithemia, uric add diathesis. — Ibid., 516. 



(Editorial.)—./. .4m. .V. .Is 



Gatch, W. D. 
Anesthesia in 
Ixix. 367-371. 



Ilium and clinic. — /. .4m. il. Ass., Chicago, 1917, 



50 



JOHNS HOPKIXS HOSPITAL BULLETIN 



[Xo. m 



Gkkaghty, J. T. 



UI4 1! 



:.l t'l: 



hi- Ki'jiiinal vesk'les in persistent nongonorrheal infections 
i 11 uretlira and l)la(ldcr. — ./. Am. M. Ass.. Cliitagi). ini7. 

ti'iMtment of bladder tumors. — lliid., Ixix, 1336-i:U2. 
iinal tests. — tioiith. .U, ,/., Birmingliani. Ala.. ini7. x. 



of the l)ladder with special reference to localized resistant 
areas of cvstitis. — Surg.. Oiiue.v. <(■ Ohst.. Cliicago, 1917. sxiv. (i.").">-i'.."i~<. 
rresent status treatment of liladder tumors. — W'ext Virii. il. ■!.. Hun 
tington, 191B-17. xi. l!):'.-inO. 



ivelocytic leuliemia by radiun 

i;fil. 

lious anemia by transfusion 

•ago, ini". Ixviii. 42n-4:i2 : i 

Ua.. 1917. X. 341. 

eventeen cases. — Surg., Giiiui 



I phlyctenules). 



GiFPiN, H. Z. 

Observations on the tre.-itmeut of ] 
riostdii M. d- S. ./.. 1917. clxxvii. ilsd 
A report on the Ireatmetit of pern 
spleni'Ctomv. — ./. Am. -1/. A.i.t.. fh 
lAbstr.l South. M. ./., BIrininghani. 
Oaeinolytic Jaundice : a review of 
Obst., f'hicago, 1917. .xxv, 152-161. 

GOETSCH, E. 

The relation of the pituitary gland to the female generative 
Suri/., (liiucc. iC- Ohst., Chicago, 1917, xxv, 229-243. 

Golbhacii, L. J. 

Lvinpha tic-nodular keratoconjunctiviti 
Ass.. Chicago. 1917. Ixix. 102-1(14. 

Goonp.\s I ri:i:, K. \V. 

All .11 i.l |ii>hrlii-oine-methvlene blue stdutiou for routine and siiec 

stiiinin- ./. Sin. M. Ass., Chicago. 1917. Ixix. 99S. 

.\ c<ini liliuiion to the study of pancreas intoxication. — /. IC.ri)rr. 

Bait.. 1917. xxv. 277-2S3 : also Stud, liockc/eller Inst. M. Ifcsi-ar 

N. Y., 1917. xxvl. 103-109. 

Crystalline hyalln. — ./. Med. licsearch. Bost.. 1917. xxxv, 239-204. 

GouilAM, L. W. 

Acute myelogenous leuljaeinia. The report of two cases with posit 
oxydase reaction. — Albany 3/. Ann.. 1917. xxxviii. 201-23.S. 

GoRTOx, W. S., and Ti.wis. D. M. 

A modified Woodyatt puni]i.^/. Irol.. Ball.. I'.iIT. i. 13.-)-13S. 

Gkky. E. G. 

The diversion of the pancreatic juice from the duodenum ini.i i 
stomach. Its eflTects uijon the level of gastric acidity ami upon i 
pancreas. — ./. EJ-per. J/., Bait.. 1917. xxvi. 82.1-S40. 

GcxDRUM, F. F., and Hale, N. G. 
Intestinal infection in the Sacrament 
Fran., 1917. xv, l.")7-158. 

Hamma\, L. 

The diagnosis of pulmonary tiilie: 

1917, i. 200-217. 

Hypertension. Its clinical aspects 



T\\ 



1".a; 



1. Dei 



lid 



to Vall.'y.— 


Cnlif. SInIc -1 


M 


"Ulosis.— .li; 


. Her. Tubci 


r.. 


— Med. riiil 


\. Am.. Phi 


a.. 


t of the me 


liastinum. 2. 


M 



:)r remove?— ft»ifn(o 1/. ./.. lOII 



•yst with calciticalion.- 



Ha.mma.n, L., and Hirschmax, I. I. 

studies on blood sugar. I. Alimenhyperglyceinia and glycosuria as : 
test of sugar tolerance.— .Ireh. Int. Med.. Chicago. 1917, xx, 701 -SOS 

Hender.sox, D. K. 

A case of pathological lying 
Psi/chkit.. Edlnb.. 1917. xv. 

Henxixotox, C. W. 

fiall bladder surgery— shall \ 
Ixxii. 41.-I-419. 

Heuer, G. .1. 

A case of intrathoracic 
Bait.. 1917. 1. 129-144. 

HlOGIN.s, H. L. 

Kffect of alcohol on the respiration and the gaseous metabolism in 
man. — /. I'harmticol. <(■ lixpcr. Thcraii.. Bait., 191(i 17. Ix. 441 472. 

HiGGixs, H. L., and M.\rriott, W. M. 

A colorimetric methoil for the determination of the CO.. perci'iitage in 
air.—./. .liH. Chim. Snc, Easton, l"a., 1917, xxxix. OS 71. 

HlXMAX, F. 

I'rological diagnosis in general practice. — Ch(i7. .s'(«(r ./. J/.. San Fran 
1917, XV, ,392-401. 

Karty diagnosis of renal tumor: with the report of ,'i ca.ses and the 
demonstration of several pyelograms illustrative of the dilhcullv — 
Surg.. Clinicc. d Obst.. Chicago, 1917. xxlv, 0(i9.0.>'0. 

HiTZROT, J. M. 

ITaemanglomn cavernosum of hone. — .inn. Surg., I'liila.. 1917 l\v 
470-4S2. ■ ' ' 

Subcutaneous Injuries of tile liver.- /Iiirf., Ixvi. .-|O-03. 
Central fracture of the acetaliuhim : nnkylosis of the hip due to bouv 

fusion l.riM n I lie ixreat trochanter and the ileum. — Ibid.. 1110-107. 

Comi'lic I di iidylar fracture of the right humerus (oldl ; arthro- 
plasty.— /I;irf., Ili7.1(kS. 

Some phases of the present treatment of fractures. — ;Voio Vort- Slate 
■J. M.. N. y.. 1917, xvll, 33,S-340. 

Hoi,>[Es, J. B. 

Becent work In aiiatc 
-4m. ,/. Uis. Child.. Chli 

HOCII, A. 

Ueeommiuidations for the observation 
the war. — I'sgehiat. Dull.. I'tlca. 1911 



ental disorders imideni to 



Hooker, D. R. 

Perfusion of the mammalian meilullu : cute on thi' action of et'ivl 
alcohol. — ./. Pharmacol. <t- Ej-per. Therap., Bait.. 1917 Is. x. 121 l_'s ' 

Hooker, D. R., and Wilsox, D. W. 

The perfusion of the mammalian medulla : the effect of carbon dioxide 

and other substances on the respiratorv and cardio-vasciilar centers 

Am. ./. Physiol., Bost.. 1916-17. xlii. 612. 

Hooker, D. R., Wilsox, D. W., and Coxxett, Helexe. 

The iM.rriisii,n of the mammalian mi'dulla : the effect of carbon dioxide 
and othi-r siilistamcs on the respiratory and cardio-vascular centers. — 
-liH. ./. Physiol.. Bait.. 1917, xliii, :;.->!. :;(;i. 

Howard, C. P., and Baumaxn, L. 

The mineral metabolism of experimental siurvv of guinea-pig. — .liii. ./. 
M. Sc, Phiia., 1917. cliii, 650-663. 

Howard, C. P., and Stevexs, F. A. 

The iron metabolism of hemochromatosis. — Arch. Int. Med.. Chicago 
1917, XX. 896-912. 

Howell. W. H. 

The coagulation of the blood. [ Abstr.]— -Vcjp York .1/. .7. [etc. 1, 1917. 
cv. S41 N42 : also I Abstr. 1 South. M. ./., Birmingtam. Ala.. 1917. x. R49. 
Physiology of secretion. — Kef. Handb. Med. Sc. N. Y.. 3d ert.. 1917. 



704. 



fChicago.] 1917. 



HowLAXD, J., and Marriott, W. McK. 

A micro niethoil for the determination of calcium and magnesium in 
blood serum. — ■/. Iliol. Chem.. Bait., 1917. .xxxii. 233-239. 

HowLAXi), J., and Marriott, W. McK. 

Treatment of acidosis in children. In: Practical treatment. ( Musser 
& Kelly.) 1917, iv, .-)00-.507. 

HcxxER, G. L. 

Surgical indications in urinary tract diseases. — Ibid.. .S56-S07. 
Further studies on ureter stricture; report of one hundred I'ases. — 
1l«.s;i. .U. Ann.. 1917, xvi. 2S1-290. 

HfBl), H. M. 

State hospitals and agricullnral preparedness. (Editorial.) — Vorf. 
Ilo.y).. St. Louis. 1917. ix, 24. 

HCRD, H. M. [AND OtIIER-S] 

The institutional care of the insane in tlie luited States and Cniiaaa 
V, iv. Bait., 1917. .lohns Hopkins Press, 652 p., S'. 

HUKWITZ, S. H. 

Etiologv and treatment of hemorrhagic diseases. — -i»i. ./. M. Sc, Phiia. 
& X. Y.'. 1917. div. OS9-707. 

Intravenous injections of colloidal solutions of ncacin In hemorrhage. 
Preliminary note. — ./. .4»i. If. Ass., Chicago. 1017. Ixviii, 099-701: also 
lAlistr.] South. M. ./., Birmingliani. Ala., 1917. x, 0S5. 

HvRwiTZ, S. H., and Whipi'le, G. H. 

■Studies on blood proteins. II. The alhumin-globnlin ratio in experi 
mental intoxications and infections.^-./. Krpcr. M.. Bait.. 1917. xxv. 
231-252. 

Hrs.sEV, R. G., Felto.x, L. D., and Bayxe-Jo.xes, S. 

The reaction of the ceri'brospinal fluid. Preliminary report on hy 
(Irogen-ion concentration as determined by the colorimetric method. — 
Arch. Int. Med.. Chicago. 1917. xix. 1085-1090. 

Jacobs, H. B. 

Fund for Belgian and French physicians. (Letter.) — J. Am. M. Ass . 
Chicago. 1917. Ixix, 2063. 

Janeway, T. C. 

Address in medicine. Slight variations from normal stnicture anil 

function, anil thi'ir clinical siguilicance. — Canud. .Med. .Iss. I 

Toronto. 1917. vli. 5.S9-00S. 

IIodi;kins disease with extensive skin eruption. — .1/crf. Clin. V. Am 

Phiia.. 1!I17. i. 1-2(1. 

Postural albuminuria. — Ibid.. 21-32. 

Diabetes associated with ilisturbances of the external secretion of tl 

pancreas in a svphilltic— /(iri/.. 33-46. 

War and medicine. — .hihns Hopkins AInmni .Mag.. Bait.. 1917. 

215-233. .... 

Hi. betes.. — In: Practical treatment. (Musser vt Kelly. 1 liHi. r 



In: 



id le 



liydrogen ion 



,00. 
lulroductorv survey of I-^ench medical scienc 
iug in France. (Chicago.] 1917. 171-174. 

Jaxnky, .T. H., and Siioiii., A. T. 

The growth of liaclllus coll in urine at var 
trations.— ./. I'rol.. Ball.. 1917. i. 211-229. 

,JELKS, E. 

Osteochondritis rteformaus juvenilis. — /. I'loridn M. Ass.. .lacksooville. 
1917, ill. 257-259: also lAlistr.j South. If. ,J.. Birmingham, .\ln., 191 i. 

cute appendicitis. — /. 
lie. 1917. iv. 37-39. 

.Jones, W., and Reap, B. E. 

Adi-nine uracil dlnucleotide and the structure of .vcnst nucleic acid.- 
■r. Itiol. Chem.. N. Y.. 1917. xxix. 111-122. ^ „, , ,„ 

The mode of nucleolid.. linkage in yeast nucleic ncld. — lbid._, 12.1-126. 
rracil-cvtosine dlnucleodde— /bid.. Bait.. 1917. xxxl. .3n-4o. 
The structure of the purine mononucleotides. — Ibid.. 33i-342. 

Kkitii, N. M., and Pti.FdRii, D. S., ,Ir. 

Experimental- hydronephrosis, functional and anatomic changes In 
the kidnev following partial ureteral obstruct ion.— -4rc/i. Int. Med., 
Chicago. 1917. xx. 853-878. 



February, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



51 



'"'Sifo'thndd nnd results, of radium treatment of uterine hemorrhage due 
?o o?her cnuts than malignancy.-rr. Am. Oynec. Soc, 1917. xlll. 

^^Thi >i(ia'al and sexual behavior of infra-human primates with some 
pg^p^rable facts in human behavior. — Paychoanahjt. Rev., Lancaster, 

Se psychology of'" The Yellow Jaclset." — Ibid., 393-423. 

icEMrF, Helen D. C. 

The preferential use of the hands in monkeys with modiflcatlons by 
traininc and retention of the new habit. — Psychol. Bull., Princeton, 
N. J., & Lancaster, Pa.. 1917, .xiv, 297-301. 

K.NOX, J. H. M., Jr. 

The value of the von Pirquet test as controlled by necropsy findings. — 

Am J Dis. Child., Chicago, 1917, xiv, 47-51. 

A case of hemorrhagic disease in the new-born treated by indirect 

transfusion. — .irch. Pediat., N. Y., 1917. xxxiv, 771-772. 

The place of infant welfare in public health instruction. — J. Am. II. 

Ass., Chicago, 1917, Ixix, 1156-1160. 

Krai'SE, a. K. 

The American review of tuberculosis. (Editorial.) — -Im. Rev. Tuherc. 

Bait.. 1917. i, 51-53. „., , „ ^ 

Undergraduate instruction in tuberculosis. — Ibid., 233-244 ; also Med. 

Standard. Chicago, 1917, xl, 315-320. 

Community studies of tuberculosis. (Editorial.) — Am. Rev. Tuberc., 

Bait., 1917, i, 114-117. ' , „ „ ,„,- 

Edward L. Tnideau : a study. — J. Outdoor Life, N. \., 191(, xiv, 

295-297. 

The "nature of resistance to tuberculosis. — New York ,1/. J., 1917. cv, 

791-792; also Am. Rev. Tuberc., Bait., 1917. i. 65-82. 

Langneckeb, H. L. 

The economic importance of the well poised person. — Calif. State J. M., 
San Fran., 1917, xv, 256-259. 

Leon.\rd, V. N., and Datton, A. B. 

Fatal complications of Percy's "Cold Iron" method in the treatment 
of inoperable carcinoma of the cervix. — Surg., Oynec. d Obst.. Chicago, 
1917. xxiv. 156-161 ; also [Abstr.) South. M. J., Birmingham, Ala., 
1917. X, 260. 

Levy, R. L. 

Facial paralysis following Pasteur antirabic treatment ; report of a case 
of facial diplegia with onset seventy-three days after the beginning 
of prophylactic inoculations. — J Am. M. Ass., Chicago, 1917, Ixlx. 
1873-1875. 

UBWItj, D. S. 

The clinical value of Ambard's coefficient of urea excretion. — Arch Int 
Med., Chicago, 1917, xix. 1-52. 

Lewis, W. H., and Lewis, Margaret R. 
Behavior of cross striated muscle in tissu 
Phila., 1917, xxll. 169-194. 

Lyman, D. R. 

When is the diagnosis of tuberculosis without positive sputum iusti- 

fled?— Boston If. <£ S. /., 1917, clxxvii, 135-138. 
MacCallum, W. G. 

An apparatus for the study of the dissociation of oxyhemoglobin — 

J. Am. M. Ass., Chicago, 1917, Ixlx, 523-524. 

McClure, R. D. 

History of transfusion of blood, report of one hundred and fifty trans- 
fusions. — /. Michigan M. Soc. Grand Rapids, 1917. n. s,. xvi 178-184 • 
also (Abstr.) Med. Rev. of Rev., N. Y.. 1917, xxiii, 774-773. 

McCluee, W. B., and Amberg, S. 

The occurrence of citric acid in urine.- 
xllv, 453-462. 



ultures. — Am. J. Anat., 



-Am. ./. Physiol., Bait, 1917 



McClure, W. B., Amberg, S., and Loevenhart, A. S. 

The Influence of oxygen upon Inflammatory reactions. — J. Pharmacol if- 

Exper. Therap., Bait., 1917-18, x, 209-236. 
^i«Orae, T. 

Cn^°i'' .?y'?P''"?^ ri"" lesions of the prostate and deep urethra.— 
Tnn^-, ^- -■^**- ■'•' Toronto, 1917, vil, 385-392. 

the calTij^i^i" enlarged liver in a young adult (primary carcinoma of 
Aortitis- ??'^"*-~^"'''''""'- ^''"■■' P'^""" 191'^. 27. s., 11, 46-55. 
other than^.™"""°° neglect of examination of the aorta for disease 
aortitis Ao«ll7^'"- , Aortitis due to infectious diseases. Syphilitic 
Clinical feature^'^ ,?°'' rheumatic fever. Illustrative case reports. 
1917. 1 195 215 D'^Snos's- Treatment.— if ed. Clin. N. Am., Phila., 
Amebic dysentery.-Proe. Path. Soc, Phila. (1916), 1917, xxxvii, 25. 
Macht, D. I. 

Im. r']?.°Vc?i?X ''ikTlt^^^'il g"^"'-'"^ "■> ""■ ''isestive tract.- 

'"firn'Tsri^^cZy^ii ^dr?:^ *'"""«'' ""^ --j"-"™.- 

A case of poisoning by musterole.-i/Md ivi,- qm 

eTc?. ThtZ^^iT'^ir^.'W <V!^,«-i tte-t"e^?is.-^. Pharmacol, d 
Polds.-/td.T9™oT.f" "' ""' "'''""■ "I- Action of the opium alka- 
H!;in''''c?t^"rS'™fnf'ln''„n^ "■"""• ^7<, Action of h.vdrastln. hvdras- 
nnalyslTof t"he\,™u';n ac?i° n -?M/''4'i'",03"'^""^''^' ""'' " *"^"'" 
^trllel.J:/\7r'4oteo°' '""^ "'"■*"• '"■'■' Action of nitrates and 

c^k,bi'natl'oTwlth'lLw?h%"^ the opiuni alkaloids individually and In 

A cCn??(K,^?i . '^IV^^ ".^^"'^ °° t'l'' K"" bladder.— /did,, 473-481 

J- ^>ot Bait" IgiV^-l.^g^Ttir^ °' '""^ "'•'^'" ""^ theVas drferens.- 



On the comparative influence of morphin and total opium alkaloids on 
renal colic. — Ibid., 201-209. 

A referat on trench nephritis. — Virginia M. Semi-Month., Richmond, 
1917, xxii, 240-241. 

Macht, D. 1., and Fisher, H. G. 

On the toxic action of opium alkaloids Individually and In combination 
with each other on Paramecia. — J. Pharmacol. <t Exper. Therap., Bait., 

Macht, D. L, and Isaacs, S. 

Action of some opium alkaloids on the psychological reaction time. — 
Psychobiology, Bait., 1917, i, 19-32. 

Major, R. H. 

The production of kidney lesions with staphylococcus aureus toxins.^ 
J. Med. Research, Bost.. 1917. xxxv, 349-356. 

The production of acute and chronic kidney lesions with Bacillus 
mucosus capsulatus. — Ibid., xxxvii, 125-137. 

Mall, F. P. 

On the frequency of localized anomalies in human embryos and infants 
at birth. — Am. J. Anat., Phila., 1917, xxii, 27-72. 

Cyclopia in the human embryo. — Contrih. Embryol. (Carnegie Inst ) 
Wash., 1917, vi, 7-33. 

Marriott, W. McK., and Haes.sler, F. H. 

Micromethod for determination of inorganic phosphates in blood 
serum. — ./. Biol. Chetn., Bait., 1917, xxxii, 241-243. 

Marriott, W. McK., and Haessler, F. H. 



Marriott, W. McK., and Hqwland, J. 

Treatment of acidosis in children. — In: Practical treatment. (Musser 
& Kelly.) 1917, iv, 500-507. 

Marshall, H. W. 



Maso.n, V. R., Sydenstricker, V. P. W., and Rivers, T. M. 

Transfusion of blood by the citrate method. — J. Am. M. .iss., Chicago, 
1917, Ixviil, 1677-1680. 

Maxcy, K. F. 

Lange's colloidal gold reaction in anterior poliomyelitis.^ — George llash- 
ington Univ. Bull., Wash., 1917, xvi, 35. 

MixcY, K. F., and Felton, L. D. 

The colloidal gold reaction of the cerebrospinal fluid in acute polio- 
myelitis. — J. Am. Asa., Chicago, 1917, Ixviil, 752-754. 

M^LOY, C. R. 

I Umbilical cord Injections, associated with B. dlphtheriae. — Grace Hoap. 



M^- 



Bull., Detroit, Mich.. 1916-17, 1. 3-7. 

Hypernephroma with case report. — Ibid., 1917-18, 11, 5-11. 

|YER, A. 
The aims and meaning of psychiatric diagnosis. — Am. J. Insan., Bait , 

I 1917-18, Ixxiv, 163-168. 
The approach to the investigation of dementia praecox. — Proc. Alien- 
ists <£ Neurol. Am., Chicago, 1917, vi, 147-151 ; also Chicago M. Rec, 
1917, xxxix, 441-445. 

Progress in teaching psychiatry. — J. Am. M. Ass., Chicago, 1917, Ixlx, 
861-863. 

Mental and moral health in a constructive school program. — In: 
Suggestions of modern science concerning education. (.Tennings, 
Meyer, et al.) N. Y,, 1917, 101-156. 

Modern conceptions of mental disease, and The problem of sex educa- 
tion.— /did., 201-211. 

MEJ.ER, G. B. 

A review of 300 obstetrical cases in private practice. — .im. J. Obst., 
N. Y., 1917, Ixxv, 798-808. 

MiNOT, G. R. 

Diminished blood platelets and marrow insutflciency. A classification 
and differential diagnosis of purpura hemorrhagica, aplastic anemia, 
and allied conditions. — Arch. Int. Med., Chicago, 1917. xix, 1062-1084. 
Hemorrhagic conditions. [Abstr.] — Boston M. <f S. J., 1917, clxxvli. 



MiNOT, G. R. and Lee, R. L 

Treatment of perniciims anemia, especiallv bv transfusion and splen- 
ectomy. — Boston M. d S. J., 1917, clxxvli, 761-775. 
The significance of blood platelets.- Ciet'erand M. J.. 1917. xvi, 65-87. 
Coagulation time of the blood in pneumonia. — .J. Am. M. Ass., Chicago, 
1917. Ixviil. 545-546. 

MnvoT, G. R., and Sellards, A. W. 

The preparation of hemoglobin for clinical investigations. — J. Med. 

Research, Bost.. 1917. xxxvii 161-170. 
MiNOT, G. R., and Wright, J. H. 

The viscous metamorphosis of the blood platelets. — J. Exper. M., Bait., 

1917, xxvl, 395-409. 
Minsk, L. D., and Sauee, L. W. 

The nonprotein nitrogen of the blood in atrophic infants. — .Im. J. Dis. 

Child., Chicago, 1917, xlil, 397-403. 

Mitchell, J. F. 

Diaphragmatic hernia. South. M. J 
561-564. 

Morris, R. S. 

Defects in enforcing the preliminary requirements in English. — J. .Im. 

M. Ass., Chicago. 1917. Ixvili. 1937. 

A comparison of the percussion and roentgen-ray findings after Injection 

of the pericardium. — Ibid.. Ixlx, 450-454. 

Tonslllectomv during course of acute rheumatic fever. — J. Lab. <f 

Clin. M., St. Louis, 1916-17. ii, 168-179. 



ilngham, Ala., 1917 



53 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 324 



MOEBISS, W. H. 

The prophylaxis of anesthesia acidosis. — J. Am. M. Aas., Chicago, 1917, 
Ixviii, 1391-1394. 

MoKRLSs, W. H., and Slemons, J, M. 

The non-protein nitrogen and urea in the maternal and the fetal blood 
at the time of birth. [Abstr.] — South. M. J., Birmingham, Ala., 1917, 
X, 160; 173. 

MOSENTHAI., H. O. 

Essential hypertension. — iled. Clin. .V. Am., Phila., 1917. i, 101-117. 
The dietetic treatment of diabetes niellitus. — Ibid., 119-130. 

MosEXTHAL, H. O., and BjVRker, L. F. 

On the control of the symptoms of diabetes insipidus by subcutaneous 
injections of extracts of the hypophysis cerebri (pars posterior and pars 
intermedia).— 4m. J. Urol, Bait., 1917. i, 449-467. 

MosENTiiAL, H. 0., and Hilleb, Alma. 

The relation of the non-protein nitrogen to the urea nitrogen of the 
blood. — J. Vrol., Bait., 1917, i, 75-89, 

MosEXTiiAL, H. 0., Hilleb, Alma, and Clausen, S. W. 

The non-protein nitrogenous constituents of normal human muscle. — 
Proc. Soc. Bxper. Biol. <t Med., N. Y., 1917, xiv, 170-171. 

Moss, W. L, 

A simplified method for determining the iso-agglutlnin group in t'le 
selection of donors for blood transfusion. — J. Am. M. Ass., Chicago, 
1917, Ixviii, 1905-1906. 

Nassau, C. F. 

Closure of fecal fistula by extraperitoneal method. — Penn. M. /., 
Athens, 1917, xx, 539-540. 

Neymann, C. a. 

Some experiences in the German Red Cross. — Ment. Hyg.. Concord, 
N. H., 1917. 1. 392-396. 

Nevma.nn, C. a., and Burrows, M. T. 

The effect of a -amino acids and peptones on the growth of cells in 

vitro.— .Im, ./. Physiol., Bost., 1916-17. xlii, 597. 

Studies on the metabolism of qells in vitro. I. The to.xiclty o' 

-amino acids for embryonic chicken cells. — J. Exper. M., Bait., 1917, 
XXV, 93-108. 

Netmann, C. a., and Gageb, L. T. 

New method for making Wassermann antigens from normal heart tis- 
sue. — J. Immunol., Bait., 1917, ii, 573-383. 

Nixon, P. I. 

Retroperitoneal hernia into the duodenal fossae. — .\nn. Surg., I'hiii.. 
1917, Ixv, 456-461. 
Novak, E. 

Hyperplasia of the endometrium. — Am. J. Obst., N. Y.. 1917, Is-v, 

996-1001, 

Abdominal hemorrhage of ovarian origin ; with report of a case i le 

to rupture of a small follicular cyst. — J. Am. M. Ass., Chicago, 19 7, 

Ixviii, lli;0-n02. 

TIm' cuKauiitherapy of menstrual disorders. — Med. d Surg., St. Loi is, 

Conginital alisence of the uterus and vagina. With report of ;ix 
cases. — Surg., Qynec. cC Obst., Chicago, 1917, xxv, 532-537. 

Opie, E. L. 

The focal pulmonary tuberculosis of children and adults. — J. Ed-per. If., 

Bait., 1917, xxv, 855-876. 

The relation of apical tuberculosis of adults to the focal tuberculo'ls 

of children.— /bid., xxvl, 263-277. 

Progressive muscular ossification (proEiresslve ossifying myositis) --a 

lirogressive anomaly of osteogenesis. — J. Med. Research, Bost., 19;7, 

xxxvl. 207-275. 
OriE, R. L., and Allison, N. 

II,\pertrophlc chondrodystrophy in infancy and adolescence — a progp'S- 

sive anomaly of osteogenesis. — J. Med. Research, Bost., 1917, xx.\,'i, 

277-294. 

Osler, Sir W. 

Iteciirrence or redeposit of cancer? — lirit. M. J., Ijond., 1917, i, 455. 
Tlie c.impaign against syphilis. — Lancet, Loud., 1917, i. 787-792; also 
lUit. M. J., Lend., 1917, i. 694-696. 

War wastage: a note of warning to examiners of recruits. — ./, .-Im. M. 
Ass., Chicago, 1917, Ixlx, 290. 

PAHriTT, C. D. 

Tuberculosis often of secondary inipi>rtance to oilier pathological con- 
ditions.— Cnnnd. M. Ass. ,/., Montreal, 1917, vll, 10-17. 

Park, E. A. 

Kxlirpadon of the thymus in the guinea-pig.-^/. E.Tiier. M . Ball,. 
1917, xxv, 129-152. 

Park, E, A., and Burrows, M. T. 

The study of a small outbreak of poliomyelitis in an apartment house, 
occurring In the course of an epidemic in a large city. — Arch. Int. Mt.tl., 
Chicago, 1917, xx, 56-78, 

Peaiiouv, F, W, 

a report of the Harvard Infantile I'aralysis Commission on the diag- 
nosis atid treatment of aeiile cases of the disease during 1916. — Iloston 
M. .0 .S-. .[.. 1917. clxxvi, c-.::7 Ii42. 

Report on the treatment of myelogenous leukemia with radium. — Ibid., 
el.xxvii. S7;i-N74. 

Cardiac dyspnea. [Abstr.]— Cnnndn Lancet. Toronto, 1917, 1, 392-395 ; 
also .Vcte Vol* Af. .r. letc.l, 19]", cv, 693-694, 

Recent aiivances In the study of heart disease and their significance 
to the irm.-iii iMMitiiioner of niedlciuo, — Wisconsin M. J., Aliiwaukee, 
I91i;-17, \v ■'■:■ -''•:■■ 

Clinical siihlir ihi. respiration. III. A mechanical factor in the 

proiluctioii cif il\s|'iira in patients with cardiac diecnse. — Arch. Int. 
Med., Chlcajjo, 1917, xx, 433-442. 



vesico-vaginal fistula. - 



IIosp. Bull, 
xvi, 266-270 ; 



Peabody, F. W., and McClube, C. "VV. 

Relation of vital capacity of lungs to clinical con<lition of nntient» 
with heart disease.—^. .4m. If. Ass., Chicago, 1917, lirti, i954.i''959^°'^ 

Peabody, F. W., and Wentworth, J. A. 

Clinical studies on the respiration. IV. The vital capacity « the i..n<r= 
443-467 '■^*'''"° '" dyspnea.— a reft. Int. Med., Chicago, "17 °|^ 

Peabody, F. W., Wentwobth, J. A., and Baekee. Bebtha I. 

Clinical studies on the respiration. V. The basal metabolism and the 
minute-volume of patients with cardiac disease. — Arch. Int Med 
Chicago, 1917, xx, 40S-478. •»>:».. 

Plaggemeyee, H. W. 
Radical opt 

Detroit, Mich., 1'.I17-1S, ii. 
Epididymotomy.— ,/. ,1/icJi. M. Soc, „ 
also Orace Hasp. Bull, Detroit, Mich 

Plass, E, D., and Wilson, D. W. 

Creatine and creatinine in whole blood and plasma. — J. Biol. Chem.. 
N. i'., 1917, xxix, 413-423. 

QUINBY, W. C. 

The action of diuretics on the denervated kidney. — .Im. J Phusiol 

Bost., 1916-17, xlii, 593. 

I'yelitis in children.- >^. Am. M. Ass., Chicago, 1917, Ixviii, 591-593. 

QiNBY, W. C, and Wixtebnitz, M. C. 

Experimental nephropathy in the dog : lesions produced by injections of 
the_bacillus bronchisepticus into the renal artery. — J. Urol, Bait., 

Randall, A. 

The gross pathology of median bar formation. — jlnn. Sura., I'hUa 
1917, Ixv, 471-475, 

Median bars as found at autopsy. — J. Urol, Bait., 1917, i, 388-404. 
Epitome of the present treatment of syphilis, — Therap. Oaz., Detroit. 
1917, xll, 764-767. 

Randoli'h, R. L., and Schmeisser, H, C. 

A clinical and pathological study of two cases of miliary tubercles of 
the choroid. — Ophth. Itec, Chicago, 1917, xxvl. 1-9. 

Rem SEN, C. M. 

Abscess of the brain; report of a case. — Charlotte (N. C.) M. J., 
1917, Ixxvi, 67-69. 

Richardson, H. B. 

Familial epistaxis ; 
95-99. 



a case report. — -ii«. J. Af. Sc, I'hila., 1917, cUv, 



RiGGS, T. F. 

Syphilitic pseudoparalysis (Parrot's disease). — Journal-Lancet. .Min- 
neap., 1917, n. s., xxxvii, 636-638. 

Rivers, T. M., Sydenstricker, V. P. W., and Mason, V. R. 

. Transfusion of blood by the citrate method. — J. Am. M. Ass., Chicago, 
1917, Ixviii, 1G77-16S0. 

Rous, P., and Jones, P. S. 

The phagocytic power of connective tissue cells. — J. Exper. M., Bait., 
1917, xxv, 189-193 ; also Stud. Rockejellcr Inst. M. Research, N. Y., 
1917, xxvl, 97-101. 

Rous, p., and Robertson, 0. H. 

The normal fate of erythrocytes. I. The findings in healthy animals. — 
J. Exper. M., Bait., 1917, xxv, 651-663 ; also Stud. Rockejeller Inst. M. 
Research, N. Y., 1917, xxvii, 163-176, 

The normal fate of erythrocytes. II. Blood destruction in plethoric 
animals and in animals with a simple anemia. — Ibid., 665-673; also 
Ibid., 177-183. 

ROWNTREE, L. G. 

The treatment of neidirltls. — In: Practical treatment 

Kelly. I 1'.I17. iv. 

The cause, i.atliol 

tant clinical man 

Renal funriinn i 

iMussrr ,v Kr|l^ I 

Urenii^i. ninhiu-j, 1 

xxxvii. r,il I'.i.". ;i 

The diafjniisis au 

Minn,, 1917, xix. 



(Musser & 

icai plivsiologv, and treatment of the more Impo' 
stations of nephritis.— /6i(f., 800-855, 
health and disease. — In: Practical tre"""*"'. 

I'.n7, Iv, 7.sii-799. 

ics ami diafrnosis.— .fouriiol-Lancct, Mi>-uyil'-. 

. .;. loua Slate M. Soc, Des .Moines 191 ■. vii. i-... 
treatment of acidosis,— S«. Paul M. J., St. Paul, 



1917 



RowNTREE, L. G., Waters, C. A., and Bayne-Jones, S. 

Itoentgenography of the lungs. Roentgenographic studies 1" living 
animals after intratracheal injection of iodofjrm emulsion.— -Ixfi. /'i(. 
Med., Chicago, 1917, xix, 53S-549. 



RUSIIMOBE, S. 

Progress In gynecology.- 
clxxvii, 726-739. 



.{ S. J., 1917, clxxvi, -lKI-7»? 



Sabin, Florence R. , ,nir ,,. 

The mi-tbod of growth of the l.vmphntlc system.— Hnrrcj/ Lect., IJio-io. 

Origin tinVrilcvHniVmVntVTf'tiu^ vessels of the,cblck and of the 

pig.-Co»(n(;. i:„:in„„l (Carncule lust.). Wash., 1917. vl. 61-124 
Preliminary note ..„ the dineivntlation "f •H<«l'ibl«'^t« ""'V ,' .% 
by which they „r,.,l,i.c l,l,.„d vssels, blood plasma i'?!."^" . "' ?,'J,-io4 
■IS seen in the living chick.- -.laaf. Hccord. Phila., 191., xlii. l.i.i-u-«- 



Samtson, J. A, 

The variations In the blood supply o 
operative Importance. — Surg., Qynec. 
339-350. 



d their ,J0salble 



[he ovarv and their ,J0ssiuie 
Obst., Chicago, 191T. xilv. 



Febkuaet, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



r^^o nrinriDles ^f acidosis and clinical methods for its study.— 

l^rva,-du\firlsitu Press, Cambridge, 1917. 117 p., S = . 

S.?Morinl rui.'ures of human spleens removed by surgical operation.— 

tjvTTARns ^- W., and Minot, G. R. 

TK preparation of hemoglobin for clinical investigations.— J. Med. 
Research, Bost., 1917, xxxvii, 161-J70. 

SHAI.LENBEKGER, W. F. 

Gvnecologlc origin of nervous manifestations. — South. M. J., Birming- 
ham, Ala., 1917. X, 797-799. 

Shabpe, W. , , „ . . 

Thp onerative treatment of hydrocephalus; a preliminary report on 
forty-one patients.— A .n. J. M. Sc, Fhila., 1917..eliii, d0:?-571. 
The nressure signs of certain intracranial conditions observable in the 
fundSs of the ,ye.-Areh. Ophth., N. Y 1917, xlvi. 820-330 
Observations regarding the operative treatment of selected cases of 
cerebral spastic paralysis due to an intracranial hemorrhage at birth — 
Internat. Clin.. I'hila., 1017, 27. s.. ill, 272-282; also Proc. Ahemsts rf 
JVeuroi. Am., Chicago, 1917. vi,75;83. ^ , -, „ „ ,„.,, 

Observations regarding head injuries. — Internat. J. hurg., N. Y., 1917. 
"vxx lS.5-143 

The' field of neurological surgery. — Med. Rec., N. Y.. 1917. xcii, 711-717. 
Recent advances in neurological surgery and especially in the diagnosis 
nrd treatment of brain injuries. — Proc. Connect. M. Soc, New Haven. 
1917. cxxv. 140-139. ^. . , , ., , , 

Observations regarding the operation of cranial decompression for 
certnin intracranial conditions. — Virginia M. Semi-Month., Richmond, 
191G-17, xxi. 523-530; 553-558. 

Sharpe, W., and Fakrell, B. P. 

Cerebral spastic paralysis due to hemorrhage. A further report of the 
first sixtv-flve cases of cranial decompression for selected cases. — 
J. Am. if. ASS., Chicago, 1917. Ixlx, 1056-1057. 

Sharpe, W., and Wteth, J. A. 

The field of neurological surgery in a general hospital.— Stirj;., Oynec. d 
Obst., Chicago, 1917, xxiv, 29-36. 

Shohl, a. T., and Jannet, J. H. 

The growth of bacillus coli in urine at varying hjilrogen-ion con- 
centrations.—/. Vrol., Bait., 1917, i, 211-229. 

SiSiSON, W. R. 

Experimental studies of the intestinal flora. — .4m. J Dis. Child.. 

Chicago, 1917, xiii, 117-127. 
SissoN, W. R., Wolbach, S. B., and Meier, F. C. 

A new pathogenic sporotri<^'"»'" r""*"' 'n a cas 

the knee followins- injury (Sporotrichum c 

Ae,ea,-cft, Bost.. 1917. xxxvi. 337-355. 

Slemons, J. M. 

How closely do the Wassermann reaction and the placental histology 

agree in the diagnosis of syphilis. — Am. J. M. Sc, Phila., 1917, cliii. 

212-218. 

A case of fetus amorphus anideus. from Department of Obstetrics and 

Gynecology, Ynle Medicil School. — Am. J. Oh.st., N. Y., 1917, Ixxv. 

749-752. 

Value of blood pressure determinations in the practice of obstetrics. — 

.7. Am. M. Ass.. Chicago. 1917. Ixix, 77.8-781. 

What is gained by the union of obstetrics and gynecology in a teaching 

hospital? — Y. T. State -J. M.. N. Y.. 1917, xvii. 307-311. 

The care of prospective mothers. — Outlook, N. Y., 1917, cxvi, 110-111. 

Slemons, J. M., and Bogert, L. J. 

The uric acid content of maternal and fetal blood. — /. Biol. Chem., 
Bait., 1917, xxxii, 63-69. 

Sle.mons, J. M., and CntTis, C. S. 

Cholesterol in the blood of mother and fetus; a preliminary note. — 
Am. J. Oist., N. Y., 1917. Ixxv, 569-575. 

Slemon,s, J. M., and Morriss, W. H. 

The non-protein nitrogen and urea in the maternal and the fetal blood 
at the time of birth. [Abstr.]— SoK^ft. M. J., Birmingham, Ala., 1917, 
X, 160; 173. 

Sloan, M. F. 

The urgent need of hospital facilities for tuberculous negroes. — South. 
•^ J., Birmingham, Ala., 1917, x, 654-662. 

Smith, >f h. 

Reorgnni.^tloji „f the civilian hospital on a war basis. War depart- 
ment does i,.jf expect civil hospitals to care for wounded soldiers and 
sailors — their duty to release scientific staffs for war, and to care for 
clviUan popul_a_t-,,[i — orders relating to interns and nurses. — Hod. Hasp.. 
262-266. 



St. Louis. 1917, tr 



Sprunt, T. p., and Basker, L. F. 

The tre.atment of some ^,5,55 of so-called " pernicious " anemia : a 
regimen tha^^hns been found helpful.— J. Am. M. Ass., Chicago, 1917. 

Stearns, T., Whipple, G. H., and Cooke, J. V. 

Proteose intoxication and injur.v of body protein. 11. The metabolism 
of .logs with duodenal obstruction nnd isolated loops of intestin!.— 
J. Exjier. M., Bait.. 1917, xxv, 479-494. 

Steiner, W. R. 

Hereditary hemorrhagic telangiectasia, with report of three fauilies 

1917"x""l"'l94"'^^9'"'^'' previously recorded.— d,<h. Int. Med.. Chicago. 
StKven.s, a. R. 

Vnlque roentgenographic demonstration of a uric acid calcu' .^ — 

■^Am. M. Ass., Chicngo, 1917. Ixviii, 1903. 

J n^ diagnosis of surgical lesions of the kidney nnd ureter, — Kf .' k 

'"■ J, [etc.], 1917, cvl. 395-398. 



53 



3NE, H. B 
The ridatlon of fistula in ano to tubercle infection. — Am.. Rev. Tuberc 
Bait.. 1P17, i, 548-559. 

i)SE, H. B., and Davis, D. M. 

j Studies on the development of toxicity in intestinal secretion. — J. 
I Bxpef. .Med., Bait.. 1917, xxvl, 687-691. 

S c-'-K. n. B., and Young, H. H. 

; ii.> .'rative treatment of urethrorectal fistula. Presentation of a 
,1, ■! ! of radical cure. — J. Vrol., Bait.. 1917, i, 289-303. 



SiROfSE 

I Esse: 

■St. I- 



tial principles in the feeding of the sick. — Interstate M. J.. 
mis, 1917. xxiv, 461-463. 
agnosis of early acute pulmonary tuberculosis. — Med. Clin., 



inn 



760. 



In^ii. ■ inn in the treatment of diabetes raellitus. Historical review. 
I'r; I des involved in the "Allen Treatment." Selection of cases. 
' ■: 4s with present methods. — Ibid., 1916-17. 11. 999-1006. 

, and Perry, Maud A. 

r the sick. A manual for physicians and patients. — W. B. 
. s Co.. Phila. & Lond., 1917, 270 p., 8°. 

KER, V. P. W., Mason, V. R., and Rivees, T. M. 
^iion of blood by the citrate method. — J. Am. M. Ass., Chicago, 
.fill. 1677-1680. 

T'VYER, W. S. 

.~"holrii>'hip in medicine. — Boston M. <f S". ./.. 1917. clxxvl. 519-524. 
'■■■•: V cions on some of the commoner deviations from the ordinary 

h in the examination of the heart of supposedly normal indi- 

-.1/rrf. Rec, N. Y.. 1917, xcl, 617-623; also [Abstr.] New York 

to.]. 1917, cv. 603-604. 

lagemenl of the early stages of hypertensive cardio-vascular 

—South. M. .J.. Birmingham, Ala.. 1917. x. 367377. 

; and practice, — Tr. Cong. Am. Phys. d Surg. (1916). N. Haven. 
-. 77-98. 

e. — In: Science and learning in France. [Chicago.] 1917. 



-MS-: 



-5. B. 
• ration in 



fiediclne. — -Yew I'orA- State -J. M.. N. Y., 1917, xvii. 



jPFcHoOF, D. 
iiUited duodenum, with especial reference to chronic duodenal obstru 
if I, in visceroptosis. — .7. .4m. M. Ass., Chicago, 1917. Ixix, 510-514. 
' V I bilfs ns a factor In the production of cardlo-vascular-renal dlsease.- 
• Luih M. J., Birmingham, Ala., 1917, x, 100-103. 



. »:elnti 
(•■■■■Kan 
'•rhir. 
f'irmi 

,-^tif) 1 

iMiro.- 
jlHl". 

WJIEK."^. 
Ilharn 

dcrivi, 



W. 

on of the glands of internal secretion to the female pelvic 
s —Am. J. Obst.. N. Y.. 1917. Ixxv. 366-372 ; also Bull. Med. d 
Fac. Mariiland. 1916-17. ix, 102-107; also [Abstr.] South. M. .J.. 
i --'hnm, Ala.. 1917. x. 817. 

"■occus septicemia with metastatic infection in one eve. — 

If. ./., Birmingham, Ala., 1917. x. 740-742. 

■.;., and Finney, J. M. T. 

.ite the patent on saivarsan. (Letter.) — .7. Am. M. Ass.. Chicago, 
Ixviii. 1572-1373. 

A. L., and Kocn, E. W. 
: icological studies of the ipecac alkaloids and some synthetic 
•Ives of cephaeline. I. Studies on toxicity. — J. Pharmacol, d 

Therap., Bait.. 1917-18, x. 73-81. 

A. L., EcKLEE, C. R., and Koch, E. W. 
lacological studies of the ipecac alkaloids and some synthetic 
tives of cephaeline. II. Studies on emetic eflFect and irritant 
. -^7. Pharmacol, d Exper. Therap., Bait., 1917-18. x. 185-197. 

.\. L., Baker, W. F., and Koch, E. W. 

itcologlcal studies of the ipecac alkaloids and some synthetic 
Uve*3 of cephaeline. 111. Studies on protozoocidal and bncteri- 
artion.-^. Pharmacol, d Exper. Therap.. Bait., 1917-1.1, x. 

L. M. 

cation of the chronic high blood-pressure cases. — --Im. J. M. Sc. 
1917. cliv. 414-424. 

■:iflcance of high pulse pressure. — J. Am. M. Ass., Chicago, 1917, 
-.•4-R26. 
'4ogy of arteriosclerosis. — .J. Lab. d Clin. Med.. Bait., 1917-18. 

"oup determinations as a preliminary step to blood trans- 
usi.n "Wisconsin M. ,7.. Milwaukee. 1917. xv. 376-379. 
,"!'■' ia : case presenting unusual feature; clinical report. — Ibid.. 
• !T xvi, 63-64. 

li A., Bayne-Jones, S., and Ro'svxtree, L. G. 

ography of the lungs. Roentgenographic studies in living 
ifter intratracheal Injection of iodoform emulsion. — Arch. Int. 
irago. 1917. xix. 538-549. 

-. > A., and Doub, H. P. 
r'>>- r. I' itgen diagnosis of polypi of the maxillary sinuses. — Am. J. 
cutge oh. N. Y., 1917. iv. 470-4.72. 
.. 0-J. E. M. 
Renal rain, modern methods of diagnosis and their interpretation. — 
Pugalo If. .J.. 1917. Ixxiil. 16. 

.^ -tud:. of the vesical orifices following perineal prostatectomy. — 
' ■ ■ Biilt.. 1917. I. 543-557. 

hypertrophy with tabes. Its diagnosis nnd management from 
Ipoint of urinary obstruction. — New York it. J. [etc.], 1917. 
149. 




of urlnnry freriucncy in .voung men. — .Vete YorJt State J. J/., 
i7. xvii. .-i.',-J .'".ns. 

f the posterior urethra ; their symptomatology, diagnosis, and 
t.~~Vcd. Rec. N. Y.. 1917. xcii. 583-585. 



54 



JOHNS HOPKD 




OSPITAL BULLETIN 



[No. 324 



Harvey Led., 1915-16. 
— J. Am. M. Ass.. C 



Welch, W. H. 

Medical education in thfe United States.— 
& Lond.. 1017, 366-382. 
The Carrel-Daliin treatment. (Letter.) 
1917, Ixix, 1994. 

Whu'ple, G. H. 

Animal experimentation and medical progress : an argumentjln surlcft 
of a bill now before the state legislature. — Calif. State J. M.,\San I (i 
1017. XV, 68-70. I I 

WiiiPi'LE, G. H., and Cooke, J. V. I 

Proteose intoxications and injury of body protein. II. The mcta i 

of fasting dogs following proteose injections. — J. Exper. M., Bait. 
XXV, 461-177. 

Whipple, G. H., Cooke, J. V., and Stearns, T. 

Proteose intoxications and in.iury of body protein. II. The metii' , i 
of dogs with duodenal obstruction and isolated loops of Intfs, 
J. Exper. il., Bait., 1917. .\xv, 479-494. 

Whipple, G. H., and Hoopek, C. W. 

Bile pigment metabolism. III. Bile pigment output and bio 'I I'll- 
lug.— .4m. J. Phi/siol., Bait., 1917. xlll. 256-263. 

Bile pigment metabolism. IV. Influence of fresh bile feeding .ton 
whole bile and bile pigment secretion. — Ihid., 264-279. '[ 

Bile pigment metabolism. VI. Bile pigment output influenced b. Ithe 
Kclc fistula.— /6id., 1!I16-17, 544-5.'J7. I 

Bile pigment metabolism. VII. Bile pigment output inOuenc. ;. by 
hemoglobin injections, anemia and blood regeneration. — Ibid., -HT, 
xliii, 25S-274. , , , a i ^ 

Bile pigment metabolism. VIII. Bile pigment output infiuenc by 
hemoglobin injection: splenectomy and anemia. — Ibid.. 275-289. i ^ 
Bile pigment metabolism. IX. Bile pigment output Influenced b.v •mo- 
gioblu injection in the combined Eck bile fistula dog. — Ibid.. 29 297. 

Whipple, G. H., and Hirwitz, S. H. 1 # 

proteins. II. The albumin-globulin ratio In t: jerU 
ons and infections. — J. Exper. if.. Bait, 1917 jcxV, 



WOOLLEY, P. G. 

A series of ruptured aortic aneurysms. — Am. /. ^uph., St. Louis IQl" 

Aortic aneurysms and dilatations. — Ibid., 5.S2-605. 

Case? of hypertrophic cirrhosis of the liver. — Ibid., 64T>,e6'' 

CarJlac aneurisms. — J. Lab. d Clin. M., St. Louis. 1916-if ji o.ii .140 

Cases of unusual aneurisms. — /did.. ,^2."i-535. ' ' '■-•*o. 

The thymus — a summary. — Ibid., 632-637. 

A case of congenital cystic kidney in which a tuberculous process ^^j 



superimposed. — Ibid.. 1917, Hi, 55-58. 
Recent literature on the pathology of 
1917, xiii, 412-414. 



ancer. — Ohio M. J., Columbus, 



Studies on bio 
mental intoxic 
231-252. 



Williams, J. W. 

Obstetrics.— D. Appleton <f Co., N. Y. & Lond.. 1917. 4th ed.. 1029 

Why is the art of olistetrlcs so poorly practised? — Lwig liland 1 

Brooklyn, 1917. xl. 169-17S. 

The abuse of Cesarean section. — Surg., dynec. d Olst., Chlcaeo 

XXV, 194-201. 

Histological studv of 50 uteri removed at Cesarean section. — .' 

Gtinec. Soe., 1917, xlli. 

Wi.nternite, M. C. 

Autopsies — their value, methods of obtaining and protection 
hospital.- ilfod. Hasp., St. Louis, 1917. viil, 36-43. 

WiNTERNiTZ, M. C, and QtaNBY, W. C. 

Experimental nephropathy in the dog: lesions produced by 
of the bacillus bronchisepticus into the renal artery. -•'. ' 
1917. 1, 139-154. 

W0I.FSOHN, J. M. 

The treatment of syphilis of the central nervous system wit 
spinal injections of mercurlaiilzed serum. — Am. J. M. KciPhlli. 
cliii, 265-273. 



WooLLEY, p. G., and Ransohoff, J. L. 

Operative cure of congenital pyloric stenosis : thymic death after seven 
months; necropsy. — J. Am. 31. Ass., Chicago, 1917, Ixvlii, 1543-1544. 

Yates, J. L., and Bunting, C. H. 

Results of treatment in Hodgkin's disease. — J. Am. M. Asa., Chicago, 
1917. Ixvili. 747-751 ; also 11 i«coii«i» It. J., Milwaukee, 1916-17, xv, 
453-463. 

Young, H. H. 

The use of; radium and the punch operation in desperate cases of 

enlarged pi4state. — Attn. Surg., Phlln.. 1917. Ixv. 633-641. 

The use of *idlum in cancer of the prostate and bladder: a presentation 

of new instruments and new methods of use. — J. Am. U. Ass., Chicago. 

1917, IxviiJ 1174-1177. 

Carcinoma ,trf the prostate: an improved technic for radical excision 

with preselvation of urinary control. — Ibid., Ixlx, 1591-1597. 

Foreword.— J'. VroL. Bait., 1917, 1, 1-2. 

The organization of a special surgical unit in a general hospital. The 

.lames Buchanan Brady Urological Institute. — Ued. Rec. N. Y., 1917. 

xci. S-13. 

The relation of chronic infections of the genitourinary tract to obscure 

internal disorders. — .Vew York M, J. [etc.]. 1917. cv. 49-54. 

The use of rndiuni in cancer of the prostate and bladder. — Radium, 

Pittsburgh, 1017. ix, 47-48. 

YoiNG, H. H., and Colston, J. A. C. 

Injuries lo the pancreas following operations on the right kidney. — 
./. Vrol.. Bait., 1917, i. 179-191. 

YoiNG, H. H., and Davis, E. G. 

Double nreter and kidney, with calculous pyonephrosis of one half ; 
cure bv resection. The embryology and surgery of double ureter and 
kidney—./. Vrol, Bait.. 1917. 1, 17-32. 

YofNG, H. H., and Frontz, W. A. 

I'reli'nlnary treatment f"' prostaiectoniv in unfavorable cases. — J. .Im. 
If Ass.. Chicago. 1917, ixvlii. 526-530; niso lAbstr.] South. M. .J. 
BlVminghnm, AIn.. 1917, x. 431-432. 

Young, H. H., and Stone, H. B. 

The operntive treatment of urethro-rectal fistula. Presentation of » 
method of radical cure.— ^. Vrol., Bait., 1917, 1, 289.303. 

Zadek, I., and Barnett, E. L. 

The Importance of the ligameuls of the ankle In correction of con 
genital clubfoot. — J. Am. St. Ass., Chicago, 1917, Ixix. 1057-1058. 



BOOKS RECEIVED. 



A Handbook of Practical Treatment. By Many Writ. 
by John H. Musser, .Jr., B. S., M. D., and Tlionu 
A. M., M. D. Vol. IV. 1917. 8°. 1000 pages. W. I'., .-uii eis 
Company, Philadelphia and London. 

Complete Index to Volumes I. II, III, and IV of Musser auft f.his 
Practical Treatment. 1917. 8°. 218 pages. W. H. S:;ti,!frs 
Company, Philadelphia and London. 

An Epitome of Mental Disorders. A Practical Ouido l< 11 

Diagnosis, and Treatment. For Practitioners, AsyJui ..ad 
R. A. M. C. Medical Officers. By E. Fryer Ballard, M. B/ J. S. 
(Lond.) 1917. 8°. 211 pages. P. Blakiston's Son Cn., 
Philadelphia. 

Nutrition and CUnieal Dietetics. By Herbert S. Carter ' A , 
M. D., Paul E. Howe, M. A., Ph. D., Howard H. Ma>»o:i, R., 
M. n. 1917. 8°. 646 pages. Lea and Fcbiger, I'lii' ifi 11 'a 
and New York. 

The Diagnostics and Treatment of Tropical Discasa. li i.. 
Stitt, A. B., Ph. G., M. D. Second edition, revised and enli ged. 
With 117 illustrations. 1917. 16°. 534 pages. 
Son & Co., Philadelphia. 



■ First Aid " to the Injured and Sick; an Advanced Ambulance 
Handbook. By F. J. Warwick, B. A., M. B. Contab., M. R. C. S.. 
L. S. A., A. K. C. Lond., and A C. Tuonstall, M. D., C. M., F. R. 
C. S., L. R. C. P. Ed. Tenth edition, revised. 1917. 16° 246 
William Wood & Co., New York. 



P. BlakI ons 



Fractures of the Lower Extremity or Base of the Radius. By 
Lewis Stephen Pilcher, A. M., M. D., LL. D. 132 illustrations 
1917. 8°. 116 pages. J. B. Lipplncott Company, Philadelj""''a 
and London. 

Pathogenic Microorganisms. A Practical Manual -"Br Students, 
Physicians and Health Officers. By Wlllisni Hallock Park, 
M. D., and Anna Wessels Williams, M. D.. assisted by Charles 
Krumwiede, Jr., M. D. Sixth edition, en'arged and thoroughly 
revised. With 209 engravings and 9 fuUpage plates. 1917. 8°. 
709 pages. Lea and Febiger, New York and Philadelphia. 

ihe Fundus OcuU nf Birds. Espr'ialUl as Viewed by the OptAfl- 
moscope. A Study in Comparative Anatomy and Physiology. 
By Casey Albert Wood. Illustrated by 145 drawines in the 
text; also by 61 colored paintings prepared for ^his work by 

Arthur W. Head, F. Z. S. 1917. ISO pages. " 

Press, Chicago. 



The Lakesif'e 



Hopkins Ho.ipitol Bullrlins arc issued 1110 



gear {foreign postage, :>0 cents), may be adihcssed to the fubUiAri^ 
mil /or fit ty cents each. Single copies may also be procured from^>i* 



.ore prii 
' THE 
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ted t>j t'le I.nnn B.M.TIMORE PRESS. Baltimore. SubscriptioM . $3 W> 
JOHUS HOPKIXS IRESS. BALTIMORE; single copies Ktll be sent oy 



BULLETIN 



OF 



THE JOHNS HOPKINS HOSPITAL 



Entered as Second-Class Matter at the Baltimore, Maryland, Postofflci 



Vol. XXIX— No. 325] 



BALTIMORE, MARCH, 1918 



[Price, 50 Cents 



CONTENTS 



Uretero- Venous Anastumosis. Witli Oljservations on Experi- 
mental Hydroneplirosis and the Blood Nitrofjcn. (Illus- 
trated.) 

By Mont R. Ri;id 

Observations on Bird Malaria and the Pathogenesis of Relapse 
in Human Malaria. 
By EuGKNK R. WniTiioRK. M. D. 

The Physician's Aphorisms: A Mcdiieval Hebrew Satire. 

Bv Harry Fbiedexwald 



Minute on the Death of Dr. Theodore C. .laneway 



Proceedings of Societies. 

The Johns Hopkin.s Hospital Medical Society 72 

Personal Observations of the Hopkins I'nit in France [.Jay 
McLean]; — Extracts from Letters from Various Members 
of the Hopkins Unit; — Adenoma of the Recto- Vaginal Sep- 
tum [Dr. T. S. Culi.ex]: — Experiences in a Base Hospital 
[Dr. THO.xrAs McCrae] :— Studies on Blood Sugar [Dr. 
Louis Ham.max and Dr. I. Hir.sciimax] ; — Blood Cultures 
in Miliar}' Tuberculosis [Dr. Mildred Clough]; — Auscul- 
tation of the Pulmonary Apices in Young Men. (Abstract.) 
[Dr. John- T. King, Jr., First Lieut.. M. R.C.] ;— On Two 
Fronts [i)r. Wilfred T. Grenfell]. 

Books Received 70 



URETERO-VENOUS ANASTOMOSIS 

WITH OBSERVATIONS ON EXPERIMENTAL HYDRONEPHROSIS AND THE 

BLOOD NITROGEN 

By iloxT U. Eeiu, 

Insfrudor in Siirgerij 
(From thf Huntcrian Laboratory of The Johns Hoitkins University) 

In tlie course of some experimental worli on the blood-vessels 
of (Jogs in which arterio-venous fistula? were made in various 
situations, it occurred to me to test the effect of auastomosina- 



the ureters with the venous system. I had particularly in 
mind the possibility that the kidneys might increase or 
decrease the toxicity of .sul)stances which they eliminate from 
the blood. In addition to this point, these experiments have 
permitted me to make some interestino; observations on the 
mechanism of the production of hydronephro.sis. 

In connection with various prolilems a great deal of con- 
tradictory experimental work has been done on the kidneys and 
ureters of animals. Brown Sequard ' thought that the kidneys 
pcssessed an internal .secretion of great importance and even 
regarded ura?mia as due more to the absence of it than to the 
retention of toxic substances. To a certain extent his idea has 
fteen supported by the work of Bradford ' and others, but by 
Pearce," who has removed as much as three-quarters of the 
total kidney substance without evident impairment to the body 
function, the presence of an internal secretion has been 
doubted. By many investigators '■ ' tlie most marked hydro- 
nephrosis has been produced l)y only partial ol)struction of the 
ureter, whereas others " have noted that complete has been as 



effectual as partial obstruction. Some ° have ob.served the 
dilation in hydronephrosis to begin near the pelvis of the 
kidney and proceed toward the point of obstruction in the 
ureter, others ' that the reverse occurs. The cause of the 
ureteral pressure in obstruction in the ureter and the effect 
of the pressure on the kidney secretion have received different 
interpretations from the various investigators.' Similarly, iu 
many other problems regarding the kidney and ureter, interest- 
ing differences of opinion exist. Most work has had to do with 
a disturbance of the kidney fuuction or the natural outlet for 
its .secretion. And these experiment* have only slight bearing 
on the big prolilems of chemistry involved in the study of dis- 
eased kidneys and experimentally impaired renal function, or 
with the transplantation of the ureters eL«ewhere than into the 
blood-stream. 

Practically all investigators '■ '• ° are agreed that dogs usually 
die in from three to five days after a doulile nephrectomy or 
the ligation of botli ureters, and that the ligation of one ureter 
is comjiatible with life for an indefinite period. Various trans- 
plantations «< the kidney and ureter have been made, but, so 
far as I know, in dogs the effect on life of single and double 
uretcro-\('iioiis anastomosis has not hitherto been attempted. 



56 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 325 



Tl)e chemiial studies in these experiments were made in the 
laboratory oi" the chemical division of the medical clinic. For 
these data and ior valuable. suggestions I am greatly indebted 
to Dr. il. 0. Moscnthal. 

Techxique 
The method of anastomosis is shown in the accompanying 
illustrations (Vide Figs. 1, 2). In all the e.vperiments the 
riffht ureter was introduced into the vena cava ; when a doulile 




p of left Ureter i 



Pig. 1. — With clamps a and B removed, the uretero-venous anas- 
tomosis is complete. V. C— vena cava. Ao = Aorta. 

anastomosis was made, the left ureter, at a later period, was 
introduced into the left common iliac vein. The abdomen was 
entered either through the rectus muscle or through a trans- 
verse incision. The ureter was blocked at a point about G cm. 
from the pelvis of the kidney, by means of a Crile clamp, and 
considerable pre.<.sure was allowed to develop iu the ureter by 
the time the anastomosis was completed. A segment of vein, 
2.5 cm. long, was carefully freed and its blood-stream inter- 
rupted by temporary ligatures or clamps. Then an opening in 
the vein which the ureter would just fill was made, and through 
it the segment of the vein was ^'ashcd free of blood with normal 
salt solution and albolene. The ureter was then divided 
obliquely, at such a distance from the bladder that it could be 
gently curved witliout kinking, and introduced into the vein 
in the direction of the blood-stream. Central to the opening 
for the ureter a half-curved needle, threaded with 00000 silk 
was introduced into the lumen of the vein and broiiijht out 



through the opening. The pointed end of the ureter was then 
caught in the suture and the needle passed back through the 
foramen into the vein and brought through the vein wall close 
to where it was first introduced. After this mattress suture 
had been tied, the ureter was pulled into the vein lumen and 
sutured to its inner wall. The clamps were then removed and 
the blood allowed to resume its course. Barely was it neces- 
sary to close the slit in the vein with a suture in order to pre- 
vent bleeding. Occasionally the adventitia of the ureter at the 
curve was sutured to the parietal peritoneum in order to pre- 
vent kinking of the ureter. All bleeding vessels were tied and 
all wounds closed with silk. 




Pig. 2. — Numbers 1, 2 and 3 show the order in which the suture 
is made. To tlie right the ureter is shown sutured to the ii^ner 
wall of the vein. 

Exi'EIUMEXTS 

The following are the complete protocols of the e.xperiments 
with the exception of the chemical findings which are detailed 
further on : 

Dog 1 

May 1. 1917. Through a right rectus incision the right ureter 
is anastomosed into the vena cava. Before this anastomosis is 
made, blood is taken from the vena cava for chemical analysis. 

May 2. The dog is iu good condition; 10 c. c. of blood are taken 
from the jugular vein. 

May 4. Except possibly for an increased thirst for water 
nothing abnormal is noted. The wound appears healthy and shows 
practically no reaction. 

May 14. Tlie wound has healed per lyrimam. The general ap- 
pearance is that of a normal animal. The api)etite is good. 

June 27. The condition of the animal seems to be perfect. There 
has been no apparent loss of weight. It has been nearly two 
months since the first uretero-venous anastomosis was made. 

Second Operation. — Through a low left rectus incision the loft 
ureter is anastomosed into the left common iliac vein. The ri.eht 
kidney on palpation seems a little large and somewhat cystic. 

June 29. The dog is drowsy, but is apparently in fair condition. 
He is taking food and water very well. 

June 30. The drowsiness is somewhat more marked. The aninnl 
still walks about and eats food. 

July 4. Por the past two days the dog has not eaten food and 
has been very drowsy. Death occurred this morning. 



AIaech, 191S] 



JOHNS HOPKINS HOSPITAL BULLETIN 



57 



Autopsy. — There is a slight superficial infection of the wound 
but no peritonitis is present. The entire right ureter is markedly 
dilated and tortuous. The left ureter is dilated for a distance of 
about 2 cm. above the point of the anastomosis. The vein at 
both points of anastomosis is patent, and no clot formation is 
present. The intravenous part of the right ureter is dilated; 
the end of the ureter sticks close to the vein wall and is patent. 
Light pressure on the kidney or ureter forces urine into the vena 
cava. The end of the left ureter is open and fluid injected into the 
ureter flows readily into the vein. 

The right kidney shows a very marked grade of hydronephrosis 
without any sign of infection. The pelvis of the kidney contains 
what is apparently clear, normal urine. The somewhat thinned 
cortex shows a normal gross picture. The left kidney is slightly 
swollen and injected, but there is no dilation of the pelvis. A 
little urine, whicli appears to be normal, is present in the pelvis. 
The capsule of both kidneys strips readily. In neither ureters nor 
kidneys is there any blood. 

Weights: 

Dog 13.5 kilos 

Heart 140 grams 

Right kidney 85 " 

Left kidney 75 

Histology of Kidneys. — Right kidney: The glomeruli appear to 
be normal. The collecting tubules stand out prominiently and ap- 
pear to be somewhat dilated. They contain no albuminous material 
nor red blood cells. The epithelium of the convoluted tubules is 
practically normal. The nuclei stain well. There is no fibrous 
tissue increase. There is no polymorphonuclear nor round-cell 
infiltration. 

Left kidney: The only possible abnormality suggested in the 
sections is an occasional slight swelling of the tubular epithelium 
and the presence of a small amount of albuminous material in the 
tubules. 

Dog 2 

May 2, 1917. Through a transverse incision the right ureter is 
anastomosed into the vena cava. 

May 7. The condition of the dog is excellent. Slie takes food 
well and shows no evidence of a toxic condition. 

May 14. The wound has healed per primam. Condition is ex- 
cellent. Animal takes food and water well. 

June 27. The dog is in perfect health. 

Second Operation. — Through a low left rectus incision the left 
uretero-venous anastomosis is made. 

June 29. The dog is drowsy, but walks about and eats per- 
fectly well. There is no unusual sweating. Oedema is not 
apparent. 

June 30. The condition is about the same as yesterday. 

July 5. For the past two days the dog has practically not eaten 
and has been very toxic. It died this afternoon. 

.lutopsy. — The animal is still warm. Both wounds are perfectly 
healed and there is no infection. 

An organizing thrombus occludes the vena cava from the point 
of the first anastomosis down for a distance of 3 cm. Below this 
a fresh ante-mortem clot extends down to the bifurcation of the 
vein and into the left iliac to the point of the last anastomosis. 
This thrombus does not occlude the vessel. 

The right ureteral orifice is pervious and empties into the vein 
just above the point of ocrli^gion by the thrombus. The entire 
right ureter is dilated and tortuous. Pressure on this or on 
the pelvis of the kidney causes urine to pass into the vein. 

The left ureteral orifice is open and water injected into the 
ureter passes readily into the vein. This ureter for 3 or 4 cm. 
above the anastomosis is dilated. 



There is a marked hydronephrosis of the right kidney which 
contains apparently normal urine. 

The left kidney, except for slight oedema and injection, appears 
to be normal. 

Weights : 

Dog 1,3.7 kilos 

Heart 150 grams 

Right kidney 75 

Left kidney go " 

Histological Examination.— Right kidney: Section shows a 
moderate dilation of the tubules, a moderate degree of swelling 
of the convoluted tubules and occasionally a somewhat atrophied 
glomerulus. No hemorrhage, no polymorphonuclear nor round- 
cell infiltration. The nuclei stain well. No thickening of the 
blood vessels is apparent. 

Left kidney: The only deviation from the normal suggested in 
the section is a slight swelling of the tubular epithelium. 

Dog 3 

May 3, 1917. Through a transverse incision the right uretero- 
venous anastomosis is made. 

May 7. The dog is bright, playful, and eats. 

May 14. The wound has healed per pn)H«m. The animal seems 
to be in perfect health. 

June 29. The single anastomosis has apparently not affected the 
health of the dog. 

Second Operation. — Through a low left rectus incision the left 
uretero-venous anastomosis is made. To palpation the right kid- 
ney is large and soft. 

June 30. The dog takes food and water. Seems to be a little 
drowsy. 

July 6. The drowsiness increased; the appetite for food and 
water disappeared, and the dog died this morning. 

Autopsy. — The wounds are clean. There is a marked hydro- 
nephrosis of the right kidney. The pelvis is distended with a 
cloudy urine. It is injected and fibrin is deposited in the calices 
of the kidney. The capsule of the kidney strips readily. The 
cortical striations are not very regular. The right ureter is 
markedly dilated and tortuous. The end of the implanted ureter 
is not pervious, but is grown over by a smooth intima. The 
intravenous portion of the ureter forms a little pouch projecting 
into the lumen. Pressure on the pelvis of the kidney or the 
ureter does not force fluid into the vein. 

The left ureter is patent and water injected into it passes 
readily into the vein. The ureter is dilated near the point of the 
anastomosis. The left kidney seems to be practically normal 
except for a possible slight dilation of the pelvis. 

Weights : 

Dog 12 kilos 

Heart 150 grams 

Right kidney 80 

Left kidney 75 

Histological Exatnination.— Right kidney. The section shows an 
extreme grade of chronic diffuse nephritis characterized by an 
extensive proliferation of connective tissue with corresponding 
compression atrophy, and obliteration of the tubular elements. 
The glomeruli show thickened capsules but no adhesions between 
the capsules and tufts, and obliterative changes in the vessels. 
Isolated areas of mononuclear and polymorphonuclear infiltrations 
are found, especially in the region of the pelvis, but these are not 
a prominent feature. 

Left kidney: The tubular epithelium is swollen and in some 
areas there is a suggestion of early degenerative changes. No 
infection. No fibrosis. 



58 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 323 



Dog 4 

May 3, 1917. Through a transverse incision the right ureter is 
anastomosed into the vena cava. 

May 7. The dog does not appear to be drowsy. He taltes food 
and water well. 

May 14. The wound has healed per primnm. The condition of 
animal is excellent. 

June 29. The animal seems to be in as good condition as before 
the anastomosis was made. 

Second Operation. — The left uretero-venous anastomosis is made. 

June 30. The dog seems to be a little toxic hut is otlierwise in 
fair condition. 

July 3. Death rather unexpectedly about noon to-day. The dog 
ate his breakfast and drank some water. 

Autopsy. — The vein is normal in appearance. The mouth of the 
right ureter is easily seen. Pressure on the ureter or liydrone- 
phrotic kidney causes urine to empty into the vein. The pelvis of 
the right kidney contains urine which appears to be normal. 

The left ureter is slightly dilated just above the point of the 
anastomosis. The anastomosis is also patent. The left kidney 
appears to be practically normal. 

Weights: 

Dog 9.9 kilos 

Heart 140 grams 

Right kidney 50 

Left kidney 70 

Histological Examination. — Right kidney; The epithelium is 
low. The ducts are somewhat dilated. No evidence of infection. 

Left kidney: There is some swelling of the tubular epithelium 
and at the pelvis a small area of leucocytic infiltration. 

Nov. 7. 191G. Throu.«]i a ri.sht rectus incision the riglit ureter 
is anastomosed into tlie vena cava. 

Nov. 15. The wound healed per primam and the dos seemed 
to be in excellent condition yesterday. Death occurred during the 
night. 

Autopsy. — The wound and peritoneal cavity are free of infection. 
Death was due to intestinal intussusception at the ileocecal valve. 

The right kidney is markedly increased in size, weighing 122 
grams. It has a reddish black appearance. The capsule is 
(Edematous and has a fibrous exudate over it. The right renal 
vessels are patent and normal. The capsule is stripped with 
difficulty, a rough red and white mottled surface being left. The 
pelvis is slightly dilated and contains a yellowish gelatinous 
material whicli extends in finger-like processes up into the calices. 
The pyramids are of a dark red color. The cortex is swollen and 
filled with hemorrliages. The striations are distinct. Tlio 
glomeruli are easily seen. 

The ureter is dilated and filled with a milky fluid. This passes 
readily into the vein through the pervious ureteral anastomosis. 

The left kidney and ureter appear to be normal. 

Histological Examination. — The right kidney shows an extreme 
grade of acute nephritis; many clumps of bacteria are present. 

The left kidney shows no infection and a normal structure. 

C'.\r 1 

October 30, 1916. The right ureter is anastomosed into the 
vena cava. 

Nov. 15. The cat seems to be perfectly normal. 

Nov. 27. Death this morning. 

Autopsy. — The body is well nourished. There is no oedema and 
no ascites. The ureter is slightly dilated and the lymphatics along 
it are distended. Tlie kidney except for a little dilation of its 



pelvis appears to be normal. The ureteral opening is patent and 
fluid passes readily into the vein. No thrombus is present in the 
vein. 

The left kidney is normal. 

The right kidney weighs 13.5 grams, the left 15 grams. No 
cause for the death of the cat is found. 

The hydronephrosis in the.se cases certainly resulted from a 
jjartial obstruction to the ureters. On the right side where the 
uretero-venous anastomosis had existed for two months tlie 
kidney in every animal .showed a marked grade of hydrone- 
phrosis which involved the entire ureter and the pelvis of the 
kidney. On the left side, where the duration of the anas- 
Hydro nephrosis 




Pig. 3. — Hydroureter and hydronephrosis after uretero-venous 
anastomosis. The right dilation has developed in about two 
months, the left hydroureter in six or seven days. Note the ascend- 
ing dilation on the left. 

tomosis was t'rnni Idur to si.\ days, tlie ureter lor a short di.- 
taiice above the anastomosis was dilated, whereas the pelvis nl 
the kiihiry was nidy slightly, il' at all. dilated (\'i(le Figs. :'.. 
I iind .M. 

it is imiiossihle to say whetlier the dilation resulted from a 
|)artial narrowing oC the ureteral oriliie. which was not very 
e\i(leiit. (ir to the resistance of the xenons blood stream. It 
has been shdwn by Keith and Snnwden ' that hydronephrosis 
will dc\el(i]i when a ureteral pressrirr u\ I'ldni 10 to :>0 e. r. of 
watei- is established by partial obstrmtion in the ureter. When 
the ureteral pressure does imt exceed "lO i.e. nl' watei'. a poly- 
uria with ileKnite modilieatinn in tlie ebaracter of the urine ex- 
creted develoiis. The kidney secretion is not totally mi|>- 



Mauch, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



59 



pressed until the enormous ureteral pressure of above 50 mm. 
of mercury is present. Bayliss and Starling ' have found the 
normal vena cava pressure to vary between 2.5 and 7 mm. Hg. 
In the left femoral vein Burton-Opitz " found the pressure to 
he 5.39 mm. Hg. It has been shown " that the inferior vena 
cava pressure varies with the alidominal pressure so that both 
remain the same. The opening of the abdominal cavity cer- 
tainly alters the venous pressure. It may be that the constant 
low pressure in the vena cava is sufficient to produce the 
hydronephrosis. 

In Dog 3, who had a complete obstruction to the ureter, 
there was a high grade of hydronephrosis, associated with a 
marked fibrosis of the kidney suljstance. The belief, based 
erroneously on the work of Cohnhoim " and other experi- 



tion for a short distance above the anastomosis, but not in the 
renal end of the ureter and probably not in the pelvis. 

Chemical Studies. — At frequent intervals, specimens of the 
blood were analyzed for their non-protein nitrogen and urea 
content. At autopsy the muscle was similarly studied, and a 
specimen of urine from the pelvis of each kidney was examined. 

The total non-protein nitrogen was determined in the filtrate 
after precipitation with trichloracetic acid, the method advo- 
cated by Greenwald " being used, except for the omission of the 
second precipitation with kaolin which was not found to be 
necessary. This procedure yields higher results than the use 
of alcohol as advocated by Folin and Denis " and in our experi- 
ence has yielded data which are more nearly correct. The urea 
nitrogen was estimated according to Marshall." The salt in 



• 


Duration of 
Anastomosis 


Fistula 


Infection 


Hydronephrosis 


Weight of 
Kidney 


Histology 


Dog 1 














Rt. Kidney 


03 day.s 


Patent. 


Xone. 


Marked, involving pelvis and entire 
ureter. 


8.-> 


Practically normal 


Lt. Kidney 


7 days 


Patent. 


None. 


Present only in distah end of ureter. 


75 


Xormal. 


Doc, 2 














Kt. Kidney 


b'3 days 


Patent. 


Xone. 


Involves pelvis and entire iireter. 


75 


Almost normal. 


Lt. Kidney 


days 


Patent. 


Xone. 


Only tlie ureter and near anastomosis. 


80 


Xormal. 


Do(i .3 














Rt. Kidney 


63 days 


Not Patent 


Present. 


Marked in pelvis and ureter. Pus 
present in urme. 


80 


Chronic diffuse nephritis, e.\- 
tensive. Moderate infection. 


Lt. Kidney 


7 days 


Patent. 


Xone. 


Only in distal end of ureter. 


75 


Xormal. 


Doc. 4 














lU. Kidney 


00 days 


Patent. 


Xone. 


Marked in pelvis and ureter. 


50 


Epithelium low. Some dilation 
of ducts. Very little change 
from normal. 


Lt. Kidney 


4 days 


Patent. 


Xone. 


Slightly dilated just above point of 
anastomosis. 


70 


Some swelling of tuhular epi- 
thelium. 


Dog 














Rt. Kidney 


S days 


Patent 


Pre.sent. 


Ureter ledematous and dilated; pelvis 
only slightly. 


122 


Extreme grade of acute 
nephritis. 


Lt. Kidney 


Not done 







Xone. 




Xormal. 



menters," is that atrophy of the kidneys follows complete liga- 
tion of the ureter. More recent investigators," ho}\'ever, have 
obtained opposite results and report hydronephrosis following 
complete ligation of the ureter. The dilation in Dog 3 may 
have resulted before the ureter became totally occluded. Yet 
the extreme fibrosis here, as compared with the other hydro- 
nephrotic kidneys, may indicate that in complete ureteral 
ligation hydronephrosis does result, but that the kidney tissue 
rapidly becomes functionless and following the absorption of 
the urine in tlic [lelvis, ultimately liccoincs contracted. 

The results of our experiments are not confirmatory of the 
ob.<ervations of those who believe that hydronephrosis begins 
near the pelvis of the kidney and descends toward the point 
of obstruction. In every instance the left ureter, which had 
been traiispliintcd for only four to eight days, showed n dila- 



the urine was estimated by the A'olhardt method, and the 
nitrogen by the KJeldahl process. 

The upper limit of normal for the non-protein nitrogen of the 
Idood under usual conditions of diet is about 40 mgm. per 100 
c. c. and 15 mgm. for the urea nitrogen. This is true for human 
Ijeings " and in our hands these figures have been equally 
applicable to dogs. After the first uretero-venous anastomosis 
the non-protein nitrogen of the blood is at the upper normal 
limit, exceeding it by a slight margin at times. It varied 
between 33 and 53 mgm. per 100 c. e. of blood for the first two 
weeks after oi>eration. The blood urea nitrogen was also 
slightly increased during this period, varying between 13 and 
26 mgm. At the end of two months the urea nitrogen varied 
between 11 and 18 mgm. Such a minimal increase may be 
regarded as due to the passage of the urine from the right 



60 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 325 



kidney into the veins and the inability of the left kidney alone 
to maintain an absolutely normal level of waste products in 
the blood during the first two weeks, and to the fact that sub- 
sequently it functionated more efficiently. 

When the second uretero-venous fistula was complete,, both 
the total non-protein nitrogen and the urea nitrogen of the 
blood rose at a very rapid rate, much as they do in dogs in 



to the rate of urea accumulation in the blood and the length 
of life of the animal, are the same whether a complete nephrec- 
tomy is done or the kidneys remain intact and excrete urine 
into the blood stream. These experiments indicate that the 
waste products of the blood in their passage through the 
kidneys are not rendered less toxic, nor is the urea changed 
chemically. It may be that some of the other waste products 



TABLE II.— ANALYSES OF THE BLOOD AND MUSCLE SHOWING THE EFFECT OF URETEROVEXOUS ANASTOMOSES 
(Values are given in milligrams per 100 c. p. of blood or 100 grams of muscle.] 

Dog 1 

















Biood 












Muscle 




5/1 


5/1 


5/2 


5/7 


5/10 


5/15 


6/27 


6/27 


6/30 


7/2 


7/4 


7/4 


7/4 


Non-Protein Nitrogen 


30 


Anasto- 
mosis, 
riglit 


42 


3.^ 


36 


1 
40 


Anasto- 
mosis, 
left 






Autopsy 


i 
446 


5S5 




8 


24 


23 


18 


22 


13 


138 


238 


305 


25.1 




* 





Blood 


Muiicle 




5/2 


5/3 


5A 


5/10 


5/15 6/27 


6/27 


6/29 


7/2 


7/5 7/5 


7/5 


Non-Protein Nitrogen 


Anasto- 
mosis, 
right 


35 


36 


32 


40 




Anastomo- 
sis, 
left 






Autopsy 


523 


460 


Urea Nitrogen 


19 


16 


13 


22 18 


88 


219 


376 


225 













Dog 3 
























Blood 










Muscle 




5/3 


5/4 


5/7 


.5/10 


5/15 


6/29 


6/29 


|v. 


7/6 


7/6 


7/6 


Non-Protein Nitrogen 


Anastomo- 

righ't 


42 


33 


36 


39 




Anastomo- 
sis, 
left 


167 

1 


Autopsy 


400 


505 


Urea Nitrogen 


24 


15 


15 ! 23 

1 


11 


308 


218 



Dog 4 





Blood 


7/4 


Muscle 




5/3 j 5/4 5/7 5/10 5/15 


6/29 


6/29 7 J 7/4 


7/4 


Non-Protein Nitrogen 


Anastomo- 
sis, 
right 


53 


40 


40 


41 




Anastomo- 
sis. 

left 196 


Autopsy 


349 


46S 




26 i la 


17 


19 


12 


222 


170 











wliicli liihiU/ral nephrectomy has been pcrrormcd. Under the 
latter condition, in three experiments, the urea nitrogen in 
the blood at autopsy was found to vary between 233 and 
321 mgm. Tliese figures are comparable to those of 349 to 
523 mgm. for the total non-protein nitrogen and 222 to 
376 mgm. of urea nitrogen found in the present series. The 
duration of life in those three nephrectomized animals was 
from four to six days, a period of approximately the same 
length as after double uretero-venous anastomosis. It would 
appear therefore that tlie results oljtained in both, in regard 



of tlic blood, .•^lu-h as the ercatin, amino-acids, etc., may lie 
modified in passing through the kidneys; however, the data 
thus far obtained arc not conclusive on this point and nuist 
be verified before any definite statement can be made regarding 
them. 

The urine analyses as shown in Table 11 present some inter- 
esting features. Dogs 1 and 2, in which there was no infection 
of the pelves of the kidney or the ureter, showed a very low 
concentration of salt and a comparatively high nitrogen con- 
tent. This was true for both kidnevs. for the side on wbieb 



Makch, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



61 



there was a distiuct hydronephrosis as the result of a uretero- 
venous anastomosis of two months' duration as well as for the 
kidney in whicli these conditions had only obtained for a few 
days. This would indicate that the urine secreted against 
pressure was not normal, but resembled that found in passive 
congestion of the kidneys." A study of the urine in dogs when 
the hydronephrosis is produced by a ureteral pressure of 12 to 
30 cm. of water shows a " polyuria, trace of albumin, dimin- 
ished output of phenolsulphothalein and delayed excretion of 
lactose."' Under almost similar conditions Lepiue and 
Porteret ^ and Schwartz ^ found that the concentration of urea 
nitrogen and sodium chloride was less than in normal urine, 

TABLE III 
Analyses of urine collected from the pelves of the kidneys at autopsy 





Amou 


It of urine 


Right 


• 
Left 


Remarks 




Eight 


Lett 


NaCl % 


N% 


NaCl % 


N% 


Dog 1 
Dog 2 
Dog 3 


75c,c. 
119 c.c. 
33 c.c. 


About 5 c.c. 
About 5 c.c. 
Small amount 


.06 
.04 
.51 


1.09 
1.20 
.48 


.02 
.05 


.97 
1.20 


Pus in pelvis of right 
kidney (Dog 3). Ureter 
not patent. Albumin, 
6 grams per liter. 



whereas Lindemann " observed that the sodium chloride 
remained unchanged. In human beings the character of the 
urine varies markedly with the degree of hydronephrosis and 
its cause. It may be normal : ''" the urea and sodium chloride 
content may be greatly reduced. It is not possible that there 
was an exchange of substances by diffusion between the urine 
in the pelves of these kidneys and the blood, as the concentra- 
tion of both salt and nitrogen in the two fluids is vastly 
different. 

Furthermore, it would appear that Dogs 1 and 2, in whieli 
the ureter was patent, had a urine of entirely different compo- 
sition from that of Dog 3, in which the ureteral opening was 
closed. The considerable amount of pus, mucus and albumin 
(6 grams per liter) distinguished this last urine from the 
former ones; the concentration of salt was much higher and 
that of nitrogen much lower, indicating that the urine was 
excreted under entirely different conditions when the uretero- 
venous anastomosis was patent than when it was closed, and 
that in all probability some urine was passing into the blood 
stream while the ureter was open. 

The average duration of life for dogs after a double nephrec- 
tomy or a double ureteral ligation is from four to five days. 
In this series it was 6f days after the second ureter was 
anastomosed into the venous system. The dogs became drowsy 
and toxic, and for a short time before death refused to eat or 
drink. Marked oedema before death was not noticed in any 
case. At autopsy one dog presented moderate oedema of both 
legs and body. ^ 

Conclusions 

1. The technique by which uretero-venous anastomosis may 
be successfully accomplished, allowing of a ureter which re- 
mains patent, is described. 

2. After anastomosis of the ureter into the vena cava the 
blood does not flow back into the pelvis of the kidney. 



3. By anastomosing a ureter into the portal or splenic vein 
the effect of the urine on these organs could be studied. 

4. Uretero-venous anastomosis leads to hydronephrosis un- 
accompanied by marked histological changes in the kidney 
the effect of the urine on these organs could be studied. 

5. The dilation of the ureter in these cases begins at the 
point of anastomosis and ascends to the pelvis of the kidney. 

6. After a single anastomosis, the life of the dog, at the end 
of two months, remains unaffected. The urea and non-protein 
nitrogen of the blood rises slightly at first but show no tendency 
to increase subsequently. When both ureters have been 
anastomosed into the systemic venous current, the blood 
urea and non-protein nitrogen continue to rise until death, 
about as rapidly as they do in cases of double nephrectomy. 

7. The hydronephrotic kidney secretes urine which is char- 
acterized by a low salt and a high nitrogen concentration. 

8. After double uretero-venous anastomosis the average life 
of the dogs in this series was 6| days. The kidneys apparently 
do not reduce materially the toxicity of the substances which 
they remove from the blood stream. 

BIBLIOGRAPHY 

1. Brown Sequard: Importance de la secretion interne des reins. 
Arch. d. phys. norm, et path., 1893, V, 778. 

2. Bradford: The results following partial nephrectomy and the 
influence of the kidney on metabolism. J. Physiol., 1898-9, XXIII, 
415. 

3. Pearce, Richard M.: Influence of reduction of kidney sub- 
stance on nitrogenous metabolism. J. Exper. M., 1908, X, 632. 

3. Bainbridge, P. A., and Beddard, A. P.: The relation of the 
kidneys to metabolism. Proc. Roy. Soc, 1907, LXXIX, 75. 

4. Cohnheim: Lectures on general pathology. Translation by 
A. B. McKee, London, 1890, 1234. 

5. Caulk, John R., and Fisher, R. F.: Experimental study of the 
effects of ureteral ligation with reference to its occlusion during 
pelvic operation. Tr. Am. Assn. Genito-Urin. Surg., 1915, X, 72-81. 

6. Adami and NichoUs: Principles of pathology. Vol. II. 

7. Bainbridge, F. A.: The effects of ligature of one ureter. 
J. Path, and Bacterid., 1906, XI, 421. 

7. Henderson, V. E.: The factors of the ureter pressure. J. 
Physiol., London, 1905-6, XXXIII, 175-188. 

8. Kieth and Snowden: Functional changes In experimental 
hydronephrosis. Arch. Int. Med., 1915, XV, 239-264. 

9. Bayliss, W. M. and Starling, E. H.: Observations on venous 
pressures and their relationship to capillary pressure. J. Physiol., 
Cambridge and London, 1894, XVI, 159-202. 

10. Burton-Opitz: Muscular contraction and the venous blood 
flow. Am. J. Physiol., 1903, IX, 161-185. 

11. Gatch, W. D.: The intra-thoracic and intra-abdominal pres- 
sures. Lancet-Clinic, 1913, CX, No. 23, 394. 

12. Cohnheim: Lectures on general pathology. Translation by 
A. B. McKee, London, 1890, p. 1234. 

13. Keen's Surgery, Vol. IV, 219. 

14. Caulk, John R.: Am. Assn. Genito-Urin. Surg., 1915, X. 

14. Bradford, J. R.: Preliminary note on atrophy of the kidney 
produced experimentally. Trans, of the Path. Soc, London, 1898, 
XLIX, 169. 

15. Greenwald, I.: The estimation of non-protein nitrogen In 
blood. J. Biol. Chem., 1915, XXI, 61-68. 

16. Folln, O., and Denis, W.: Protein metabolism from the 
standpoint of blood and tissue analysis; on uric acid, urea, and 



62 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 325 



total non-protein nitrogen in human blood. J. Biol. Cliem., 
1913. XIV, 29-41. 

17. Marshall, E. K.: A rapid clinical method for the estimation 
of urea in urine. J. Biol. Chem., 1913, XIV, 283-290. 

IS. Mosenthal, H. 0. and Hiller, A.: The relation of the non- 
protein nitrogen to the urea nitrogen of the TDlood. J. Urol., 
1917, I, 75. 

19. Mosenthal, H. 0.: Renal function as measured by the elim- 
ination of fluids, salt and nitrogen, and the specific gravity of the 
urine. Arch. Int. Med., 1915, XVI, 733. 



20. Lepine and Porteret: Sur la composition de I'urine secretes 
pendant la duree d'une contre pression exercee sur les voles 
urinaires. Compt. rend. Acad. d. Sc, 1S88, CVII, 74. 

21. Schwartz, Leo: Ueber Harnveranderung nach Ureter- 
belastung. Zentralbl. f. Physiol., 1902, XVI, 281. 

22. Lindemann, W.: Ueber die Wirlvung der Gegenriickerhohung 
auf die Harnsecretion. Beitr. z. path. Anat. u. allg. Path., 1897, 
XXI, 500. 

23. Keen's Surgery, Vol. IV. 

23. Sollman, T., Williams, W. W. and Briggs, C. E.: Experimental 
atresia of the ureter. Jour, of Exp. Med., 1907, IX, 71. 



OBSERVATIONS ON BIRD MALARIA AND THE PATHOGENESIS OF 

RELAPSE IN HUMAN MALARIA' 

By Eugene E. Whitmoee, JI. D., 

Lieut.-Colonel, Medical Corps, U. S. Army 

(From the Department of Pathology, Army Medical School Washinnloii. D. C.) 



The study of iufeetious diseases in certain of the lower 
animals has given us a large amount of information regarding 
infectious diseases in man ; and this has been especially so in 
the case of infections with protozoa and worms. By taking 
advantage of the parallelism of such infections in man and the 
lower animals one has a constant supply of fresh material, 
and can carry out inoculation experiments which are im- 
portant in study as well as in teaching. 

In the study of human malaria, important information has 
been obtained from the study of bird malaria. Ross worked 
out the cycle of Proteosoma in mosquitoes when it was not con- 
venient for him to work on human malaria. MacCallum first 
observed the fertilization of the macrogamete by the micro- 
gamete in Haemoproteus. In both cases the work was later 
confirmed for the human malarial parasites. 

My object in undertaking this study was to try to correlate 
the points we know in the life cycles of various parasites of the 
red blood cells ; and to try, in that way, to get an explanation 
of relapse in human malaria. Proteosoma closely resembles 
the human malarial parasites, and it is convenient to work 
with; for these reasons I chose Proteosoma for my work. 

lUuD JI.\L.\1!IA 

From the work of Schaudinn, Novy and ifaeXoa], the 
Sergents, and Aragao, it appears that more than one type of 
life cycle may be included in the present genus Haemoproteus. 
Aragao's work has given us an understanding of the cycle of 
Hffimoproteus columbse in the vertebrate host. 

In Haemoproteus columba; schizogony takes place in the 
leucocytes (or endothelial cells) in the internal organs, espe- 
cially in the lungs. Only gametocytes are found in the red 
blood cells ; a bird once infected is proof against further infec- 
tion ; and the infection is not transmissible by injection of 
l)lood. The infection is transmitted by a hippoboscid fly. 



'Read at the meeting of The Johns Hopkins Medical Society, 
December 3, 1917. 



Thus we see tliat while HiEmoproteus is well suited for 
studying the behavior of the gametocytes, it differs from 
human malaria where both the schizonts and gametocytes are 
in the red blood cells, and the disease is transmissible by injec- 
tion of blood. 

On the other hand, Proteosoma is like the human malarial 
organism, in that the schizonts and gametocytes are in the 
red blood cells, the infection is transmissible by injection of 
blood, and the intermediate host is a mosquito. 

In the earlier study of Proteosoma it was considered that 
the schizonts persisted for a considerable time, but that they 
finally disappeared and the bird was immune. 

Wasielewski showed that the schizonts persisted in the blood 
for from 3 to 5 or even from to 11 months, because it was 
found possible to transmit the infection by injections of blood 
up to that time. From a bird in which parasites could not be 
fotmd in the peripheral blood, 0.15 c. c. of blood divided 
among three birds infected only one. Wasielewski also found 
that the parasites were more numerous in the heart's blood 
than in the peripheral circulation. 

Moldovan showed that occasionally birds recovered as early 
as one month after injection, but that usually there was a 
chronic infection up to six months with all stages of the para- 
site in the peripheral blood. 

One of my problems was to determine whether the parasites 
were constantly in the peripheral blood in a form in which the 
infection could be tran.smitted by injections of blood; and. if 
so, how long they remained there. 

The work was done with a strain of Proteosoma that was 
obtained from sparrows in New York in August, 1913, and has 
been carried in canaries up to the present time. This strain 
was obtained and used primarily for teaching purposes. 

The method of procedure was to take blood from a wing 
vein of the infected bird, dilute it with physiological salt solu- 
tion and inject it into the thoracic cavity and into the breast 
muscles of a clean bird. Parasites can be found in the 
])eripheral blood up to four or five months after infection : 



.MAKCir. litis] 



JOHNS HOPKINS HOSPITAL BULLETIN 



63 



after that I have rarely sueccedeil in finding- them. But 
peripheral Wood from an infected bird, when injected into a 
clean Ijird, has always transmitted the infection. Peripheral 
lilood taken from a number of infected birds from month to 
month and injected into clean birds has not once failed to 
infect. The longest I have been able to follow the infection 
in any birds was in three birds for 29 months from the time 
of their infection. These birds were injected on May 14, 1914, 
and the last transference of blood from them was on October 
12, 1910. During this time, many birds were injected with 
blood from the wing vein of these birds, and in every case the 
injected bird l)ecame infected. All birds injected with 
blood from these birds on the latter date became infected. All 
three of tlie old birds died before the time for another blood 
Iransfercncc. 

From this work it appears that the parasite of bird malaria 
is constantly in the peripheral circulation in a form which will 
transmit the infection on direct injection into clean birds : 
and that this form of the parasite is present for at least 29 
months after infection. 

Ijijiuxity 

Fioiuid np with this is the cjuestiou of imnnuiity. Koch. 
IJngo and others were of the opinion that one attack of Pro- 
teosoma infection conferred immunity, and that the increase 
in number of cases of the di.sease in the spring eould not l)c 
accounted for by relapses. 

Wasielewski did not agree that there -was immunity. After 
the injection of blood from infected birds into birds whose 
peripheral blood had been free from parasites for 4 days, 14 
days, 3 months and 9 months, he was able to find on the fifth 
day a few parasites in the peripheral blood of the supposedly 
recovered birds. In three birds the number of parasites was 
so small that it was even possible they were only the injected 
parasites : the fourth bird showed from 20 to 30 parasites in 
sjiecimens taken from the eleventh to the fourteenth day. 
Wasielewski was not sure whether the case was one of a mild 
relapse or of a mild new infection; but he did consider that it 
showed the bird was not immune. 

Jloldovan showed that recovered birds were susceptible to 
infection just as much as birds that had never been infected, 
but chronically infected birds were resistant against super- 
infection. 

IaELAI'SE 

In chronieally infected liirds there is not much change in 
the number of parasites in the peripheral blood, and spon- 
taneous increase of the number of parasites has not been 
observed. Wasielewski often noted an increase in the number 
of parasites in the blood of his birds during intercurrent infec- 
tions of Eome other sort. 

Moldovan was able to produce relapses by the injection of 
blood of rice-birds ; it made no difference whether or not there 
were parasites in the l)lood of the rice-birds. 

In Wasielewski's e.xperiments which he considered as show- 
ing that there was no immunity in recovered birds, he got only 



a few ]iarasites in the peripheral blood of the supposedly re- 
covered bird after an injection of Proteosoma material. But 
Moldovan showed that recovered birds developed a rich infec- 
tion and in the usual time, just as did fresh birds, after an 
injection of Proteosoma material. 

I injected blood from one 29-month infected bird into 
another 20-mouth infected bird. On the twentieth day one 
parasite was found in the peripheral blood of the injected bird. 
A previous injection of blood from each bird into a clean bird 
showed that the peripheral blood of both birds contained Pro- 
teosoma in a form that would transmit the infection to clean 
birds in the usual way. 

One l)iv(|, wliicli had been injected with Proteosoma four 
months previously, showed one partly grown parasite in the 
peripheral blood in a 10-minute search with a 1/12" objective. 
This bird was given an injection of blood from a clean bird. 
On the fifth day this bird showed no parasites in the peripheral 
blood on a similar search; on the twelfth day it showed one 
parasite in the peripheral blood on a similar search : this bird 
died on the seventeenth day, before another examination was 
made. 

At the same time, the clean bird used in this experiment 
was given an injection of blood from the infected bird used 
in this ex])eriment. On the fifth day this bird showed no 
parasites in the peripheral blood in a 10-minute search with 
a 1/12" objective ; on the twelfth day it showed a few parasites 
in the peripheral blood ; and on the seventeenth day there was 
a rich infection. 

One bird that had been injected with Proteosoma four 
months previously showed no parasites in the peripheral blood 
in a lO-minute search with a 1/12" objective. This bird was 
given an injection of human blood. On the fifth and twelfth 
days it showed no parasites in the peripheral blood on a similar 
search: on the seventeenth day there was a fair number of 
parasites in all stages of development in the peripheral blood. 

One bird that had been injected with Proteosoma 21^ 
months previously showed no parasites in the peripheral 
blood in a 10-minute search with a 1/12" objective. This bird 
was given an injection of human blood. On the fifth, twelfth 
and seventeenth days, this bird showed no parasites in the 
peripheral lilood in a 10-niinute search with a 1/12" objective. 

SUMJIAKT 

Thus it appears: (1) that in Proteosoma the usual thing 
is for the bird to develop a chronic infection which may last 
at least 29 months; (2) that all stages of the asexual cycle 
are found in the peripheral blood as long as any parasites are 
found there; (3) that the parasites are constantly present in 
the peripheral blood for at least 29 months in a form that will 
transmit the infection by the injection of blood; (4) that 
relapse occurs as a result of lowered resistance from inter- 
current infections, or of the injection of foreign blood; and 
(5) that immunity lasts only as long as the bird remains 
infected. 



64 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 32.: 



Discussion 
- Is the asexual cycle iDresent in the peripheral blood through- 
out the infection? Since the asexual cycle is present as long 
as we are able to find any parasites, it is very probable that it 
is there throughout, but is not found on account of the short- 
comings of our methods of direct examination. 

Then, the fact that the infection is transmissible throughout 
the course by the injection of peripheral blood makes it prob- 
able that the asexual cycle is present in the peripheral blood 
throughout the infection. In a Hsemoproteus infection, m 
which schizogony takes place in the internal organs and only 
the gametocytes are present in the peripheral blood, the infec- 
tion is not transmissible by the injection of blood. The same 
difference holds for Babesia and Theileria : in Babesia the 
schizogony takes place in the red blood cells, and the infection 
is transmissible by the injection of peripheral blood ; while m 
Theileria the schizogony takes place in the internal organs, 
only the gametocytes are present in the peripheral blood, and 
the infection is not transmissible by the injection of blood. We 
shall get some further help on the question from a study of 
human malaria ; and the question of some special or resistant 
form of the parasite can be taken up then. 

Human Malakia 

When we come to study human malaria, we do not have the 
assistance of animal inoculations. But we are able to study 
the peripheral blood some months after the last attack of 
malarial fever ; and in this way we may get at the question of 
whether the asexual cycle continues during the period between 
relapses. 

It is not unusual to find gametocytes in the blood of man 
several months after the last attack of malarial fever ; and as a 
result of finding parasites in the blood of men in the spring, 
before mosquitoes are able to transmit them, we have come to 
the belief that man and not the mosquito carries the malarial 
parasite through the winter. Gametocytes are commonly 
found in the blood of these " carriers " in the spring ; and it is 
generally agreed that the gametoc}i;es are intracorpuscular. 

Eowley-Lawson holds that the human malarial parasites are 
extracorpuscular and that they migrate from one red cell to 
another. The sporozoa are intracellular parasites. Aside 
from the points in human blood that indicate the malarial 
parasites to be intracorpuscular, there are some points in other 
parasites of the red blood cell that would indicate that the 
malarial parasite is intracorpuscular. Proteosoma crowds the 
nucleus of the red blood cell to one side as it grows ; Hajmo- 
proteus curves around the ends of the nucleus of the red blood 
cell as it grows ; the hEemogregarines curve around the ends of 
the nucleus of the red blood coll, coil up beside it, or crowd it 
to one side, as they grow. 

The lowest estimate of the rate of death of tlie red blood 
cells would make the life of a red blood cell 55.5 days. Other 
estimates would make it as low as 23 days. 

Since we do not believe that the gametocyte is able to travel 
from one red blood cell to another, we must conclude that any 



gametocyte found came from a schizont less than two months 
before. So, if gametocytes are found in the blood six or eight 
months after the last attack of fever we must conclude that the 
schizogony continued for at least four to six months afttr the 
last attack of fever. 

Craig found malarial parasites in the spleen of patients who 
had died of some disease other than malaria, and in whom 
there were no symptoms of malaria. The parasites were 
undergoing normal schizogony in the spleen, but in numbers 
insufBcient to produce clinical symptoms. 

It appears, then, that in human malaria, just as in bird 
malaria, schizogony continues for a long time in the chronic 
infection. Wliether the schizogony continues in the peripheral 
blood or in the blood in the internal organs makes no differ- 
ence in the part it can play in relapse. 

Theories of Relapse 

There are several theories as to the pathogenesis of relapse 
^in malaria. 

\1) Schaudinn considered that relapse was due to par- 
thenogenesis of the macrogametocytes which persisted in the 
blood and internal organs of the patient. 

iloldovan says that he undertook his experiments in order 
to determine whether relapse was due to parthenogenesis of the 
macrogamete as claimed by Schaudinn. He says that the 
establishment of tlie continuation of the asexual cycle of Pro- 
teosoma in the chronically infected birds made it unnecessary 
for him to study the question further along that line. 

In Proteosoma, the asexual cycle takes place in the peripb 
eral lilood, the infection is transmitted by injection of periph- 
eral l)lood, relapse occurs, and there is no immunity." In 



= Since writing this I have read Sergent and Hempl's article in 
Bull. Soc. path, exot., 1917, X, 550, Sur I'immunite dans le 
paludisme des oiseux. 

Proteosoma-containing material was injected intraperitoneally 
into five canaries, at least two and one-half years after their 
original infection. One of the birds developed a severe infection, 
as did two controls. In one of the injected birds, no parasites 
were found after the injection, in three of them an occasional 
parasite was found. Sergent and Hempl conclude that, in four of 
the birds, a relative immunity had persisted tor at least two and 
one-half years. 

It is my opinion that had they injected blood from the five 
canaries into other canaries, they would have found tliat the four 
resistant birds were still infected, hibile infection, and the bird 
which developed a rich infection was the only one that had 
recovered from the infection of over two and one-half years 
before. The occasional parasites found in the blood of three of the 
resistant birds were the ones that regularly circulate in the 
peripheral blood of birds that have a labile infection, and the 
parasites were found as a result of the prolonged search made "< 
this time; or there may have been a mild relapse as a result o^'the 
injury on making the injection. 

Since superinfection is not possible in labile infection, which is 
so common in protozoan infections, failure to infect hr Injection of 
infectious material cannot be interpreted as mesning immunity 
in these infections. Recovery must be determined by injection of 
blood from the supposedly recovered bird into a susceptible bird. 

The conditions as to immunity and reinfection in syphilis are 
parallel witli the conditions here. 



March. 1918 | 



JOHNS HOPKINS HOSPITAL BULLETIN 



65 



Hsemoproteus columbae, the asexual cycle takes place in the 
internal organs, only gametocytes appear in the periplieral 
hlood, and the infection is not transmitted by injection ol' 
juripheral blood ; the question of relapse or recovery with 
sterile immunity is not cleared u]) : but a l)ird once infected is 
proof against further infection. 

In the family Babesioe we have life cycles similar to those 
of Proteosoma and Haemoproteus columba?, and here the ques- 
tion of relapse and immunity is worked out. In Babesia, the 
asexual cycle takes place in the peripheral blood, the infection 
is transmitted l)y injection of periplieral blood, relapse occurs, 
and there is no immunity; just as in Proteosoma. In Thei- 
leria. the asexual cycle takes place in the internal organs, (jnly 
gametocytes ap])ear in the peripheral blood, the infection is 
not transmitted by the injection of peripheral hlood. rehijjse 
does not occur, and tliere is immunity. 

Jleyer, writing of African coast fever in cattle, says that it 
is impossil)le to infect a cow witli blood containing gamctn- 
cytes; that when an animal has had the disease, the ganic- 
tocytes and developmental forms disappear from the blood and 
the organs; that such an animal is no longer a "carrier" of 
the parasites, and does not suffer relapse. These facts, he says. 
UiTig known, are explained by Gonder's investigations, which 
show that partlienogenesis does not occur in Pirosoma parvuni 
( 'I'lieileria ]iarva). He says that, in this. Pirosoma ])arvuiii 
(Theileria ]iar\ii| is an cxccjitiun from ill! otiicr knciun 
]jirosomes. 

Schaudiiin's work has iiot hccn satisfacturiiy conlirined. 
Ami ill 'rhcilrria. the imly oi'ganisni sii far wcirked out in 
winch it was possible ti) work with persisting gametocytes 
witliout confusion from a continuation (if the asexual cycle, 
it lias lieeii necessary to niite an exception to Schaudimrs 
theory. 

(2) Tlie theory of a resistant form of the parasite has 
lieen |iut forward liy Celli, Craig, and recently liy James. 
Ill iKiiie dl' its forms is tiiis tiieory consistent with any iden 
that tlie resistant or resting organism is intraeorjniscular. on 
account 'd' tlie short life of the red blood cell. Again, siiuc 
gametocytes a]ipear in the hlood for months after the last 
attack of malarial fe\er. we know that the asexual cycle is 
going on. If it is consideretl that the resistant form of the 
]jarasite is extracellular, or is in some cell other than the red 
blood cell, we can only answer that no evidence of such a fcnni 
has been found in Theileria, the only organism so far worked 
out in which there is not confusion from a continuation of the 
asexual cycle. 

James" statement of the theory of a I'esistant or resting 
stage is as follows : 

1- In instances of true relapse, as distinguished from recrudes- 
cence, Uie first forms of tliP parasite present in tlie peripheral 
blood are large forms which, if seen during the course of an 
ordinary attack, would certainly be classed as gametocytes, though 
it might not be easy to say definitely to which sex they belong. 
These forms, and the pre-sporulating forms which follow them, 
are found before the patient has any symptoms, or is aware that 
an attack is impending. 



2. In cases which relapse during, or very shortly after, vigorous 
quinine treatment by the mouth or Intravenously, prolonged 
search of the peripheral blood may fail to show the presence of 
parasites, but examination of films of splenic blood may reveal, 
as if " encysted " in dehemoglobinized red blood corpuscles, 
(a) large forms resembling gametocytes with a voluminous 
nucleus; (b) similar forms with the nucleus divided into three 
or more separate blocks. 

These are persistent forms upon which quinine given intra- 
venously is inoperative, and, tailing a better explanation, one 
assumes that they are the cause of the relapses, and that they are 
not gametocytes, but are asexual forms in which the parasite lays 
up during the intervals between true relapses. 

If no i)arasite can stay in a red blood cell more than two 
months, it does not appear that we can accept James" sugges- 
tion that the parasite lays up in a red cell during the interval 
between relapse. He is probably right in saying that they are 
asexual organisms, but they must go through their cycle in 
less than t^\'o months or he lost. 

James' description of these parasites sounds like Prowazek's 
statement regarding the parasites that are found in chronic 
bird malaria. Prowazek .says that, while in chronic human 
malaria we find mainly gametes, in chronic bird malaria we 
also find young parasites of which one is not able to .-ay whether 
they are young schizonts or gametes. 

Jloldovan's statement that if we can demonstrate the con- 
tinuation of the ase.xual cycle we do not need to .study the 
question of whether relap.se is due to parthenogenesis of the 
macrogametocyte applies equally to the tiieory of a resistant 
or resting form of the parasite. 

Intracorpuscular conjugation, as de.scribed by Craig, can be 
interpreted as a method of keeping the a.sexual cycle active as 
readily as a method of producing a resistant form of the 
organism. \\'e know that asexual reproduction can go on for 
years in various protozoa, as .shown especially for Paramoecium 
by Woodrulf and Erdmann. The .strain of Proteosoma with 
which I have worked has been carried for over four years 
without going through an arthrojiod host. That some nuclear 
rearrangement takes jilace s(>ems to be very ju'obable. and 
intracoi-piisciilnr conjugation of |ianisites may lie of the same 
nature. 

(3) Bignanii states that — 

in all probability relapses, whether at short or long intervals, or 
whether separated by lengthy periods of latency, should be con- 
sidered from a single viewpoint; that is to say, as having the 
same genesis, depending on the persistence of the pyrogenous 
cycle. In one group of relapses the parasitic material that main- 
tains the infection is represented by a minimum quantity of forms 
of the ordinary fever-producing cycle, often recognizable by an 
accurate microscopical examination, at least at some time in the 
course of the infection, which forms for a long time cannot attain 
the quantity or the virulence necessary to cause fever. Espe- 
cially in those cases in which a series of relapses occur at longer 
or shorter intervals without quinine treatment, one should keep 
in mind the possibility that after a series of febrile attacks the 
organism acquires a certain immunity in respect to the pyro- 
genic action of the parasites; which immunity being transitory, 
as happens in other infections, it is attenuated or ceases after a 
certain period of apyrexia; whence the onset of relapse. 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 325 



But there is also a group of relapses, in which the material, 
which maintains the infection during the period of latency, is 
represented by forms resistant to quinine, due to a process of 
selection under the action of the alkaloid, as occasion offers; it 
is not necessary to suppose that such forms differ morphologically 
from others as I. myself, more than once, have also thought. 

Ill my opinion, all of the findings arc in keeping with 
I'igiiiinii's view; that is, that the asexual cyele jiersists during 
the period between relapses: that during the period between 
reln])ses the organisms are present in too small nunilier to 
produce symptoms or to be found in the peripheral blood : and 
that when something Iiappcns to reduce the resistance, tbis 
cycle l)ecoracs more active, and the organisms l)ecome numer- 
ous enough to produce .symptoms and to be found in the 
|ieripheral blood. 

The continuation of the asexual cycle over long periods in 
which tliere is no clinical malaria is undoubted. ]?elapse does 
not occur in infections with the only organism worked out 
under conditions where it is possible to observe persistence of 
gametocytes. Xo resistant or resting intracorpuscular form 
of the organism can exist for more than 50 1o (;0 days, on 
aceoniit of the short life of the red blood cell. 

IJignanii considers that there is some change in the bio- 
liigical ]ii'(i|i('rtics 111' the organisms that carry on tlie low grade 
asexual cycle and are resistant to quinine. I believe (bat tlii'i'c 
is something more to the iniinunity of the host than "in i'es|ieet 
lo the ])yrogeiiic action of the parasites."' That is. I Tliiiik 
there is more than iniuiunity to the /laroxijsnuil Inxln. Seliill- 
ing is of the opinion that the paroxysmal ioxins do not luuc 
any ajipreciable antigenic action. In cases not treated, not 
only do the attacks of fever become milder and finally cease, 
but the parasites become fewer and fewer in the periplieral 
blood. This is readily followed in Proteosoma infection of 
birds, and is a common observation in human malaria. Then, 
in Proteosoma, tlie infected bird is resistant to superinfection, 
even though no parasites can be found in the peripheral blood. 
I lielieve that antibodies are produced which actually oppose 
tbe growth and inultiplication of the parasites: that in some 
eases this opposition is strong enongli to actnally destroy the 
parasites and recovery results; that more commonly the oppo- 
.-ili<iii is not strong enough to destroy the parasites, but a few 
i>r tbeiii become resistant and keep up the cycle — what Schill- 
ing calls labile iiiferlli)n (Plehn's lolernnce). Here tlie 
animal resists superinfection. When anything occurs to lower 
the resistance of tlie host, these parasites multiply rapidly and 
set up a relapse. Here, as in so many other protozoan infec- 
tions, the antibody production continues only as long as the 
infection exists: as soon as the infection ceases, the stimuhis 
to antibody jirodnction is wiilidrawn. and the animal is asaiii 
>iisc(>ptible to infection. 

Conclusion 
In malaria, tbe body produces antiliodies which resist the 
niiiltiplieaticjii cd' the parasites. But certain of the parasite^ 
become resistant to these antibodies (or to quinine) and cmi- 
tinue the asexual cycle, the number of parasites, however, 
bidng too small to pnnlnee symptdins. When anything lia]i- 



peiis to lower the resistance of the Ijudy. these parasites are 
able to multiply rapidly and produce symptoms; that is, a 
ludapse. The continuation of gametocytes is due to th&^on- 
tinuation of the asexual'cycle. As long as the infection cov- 
tinue.s, the body is stimulated to produce antiiiodies, and the 
infected person is resistant to superinfection; that is, there is 
a labile infection. There is no immunity after recovery: as 
.soon as the infection is stopped by the antibody production, or 
by treatment, the stimulus to antibody production is with- 
drawn, anil the ]ierson is susceptible to reinfection, just as 
though be had never been infected b(d'ore. 

REFERENCES 

Aragao. II.: Uober den Entwicklungsgang und die Vebertra- 
gung von Hanioproteu.s columbie. Arch. f. ProtLstenk., 190S, Xll. 
154. 

Aragao, H.: Researches on Hnenioproteus columba;. Brazil 
Medico, 1916, XXX, 353. 

Bignami, A.: Concerning the Pathogenesis of Relapses in 
Malarial Fevers. Southern Medical Journal, 1913 (Feb.), 80. 
Translated from the Proceedings of the Society for the Study of 
Malaria, Rome, Vol. XI, 1910, by W. M. James. 

Craig, C. F.: The Malarial Fevers. Wni. Wood & Co., Xew 
York, 1909. 

Gonder, R. : Die Entwicklung von Theileria parva, deni 
Erreger des Kiistenfiebers der Rinder in Afrika. Arili. I', i'rotis- 
tenk., 1910-11, XXI, 143. 

James, S. P.: The Intravenous .Administration of Quiiiini' 
Bihydrochloride in Malaria, and a Remark upon the Form of the 
Parasite in True Relapses. Jour. Royal Army Med. Corps. Lon- 
don, 1917, XXIX, 317. 

Manson. P.: Surgeon-Major Ronald Ross's Investigations on 
the Moscjuito-Malaria Theory. Brit. Med. Jour., 1S98. I, 157."). 

Manson, P.: The Mosquito and the Malaria Parasite. Brit. 
Med. Jour., 1898, II, 849. 

MacCallum, W. G.; On the Flagellated Form of the Malarial 
Parasite. The Lancet, London, 1897, II, 1240. 

MacCallum, W. G. : On the Ha?matozoan Infections of Birds. 
Jour, of Exper. Med., 1S9S, III, 117. 

Meyer. K. F. : Afrikanisches Kiistenlieber. Handbuch d. path. 
Mikroorg.. KoUe u. Wasserniann, Zweite Auflage, 1913, VII, 544. 

Moldovan, J.; Ueber die Immunitatsverhaltnisse bei der Vogel- 
malaria. Centralbl. f. Bakt., I Abt., Orig., 1912, LXVI, 105. 

Novy. F. G.. and MacNeal, W. J.: Trypanosomes and Bird 
Malaria. American Medicine, 1904, VIII, 932. 

Prowazck, S. v.: Die Malaria der Vogel. Ilaiulbuoli d. p:itli. 
Protozoen. 5. Lieferung, 1912, 594. 

RowleyLawson, M.: A Stage in the Migration of the Adult 
Tertian Malarial Parasite. Evidence of the Extracellular Rela- 
tion of the Parasite to the Red Corpuscle, Jour. Exper. Med., 
1914, XIX, 450. 

Rowley-Lawson, M.: Free Malarial Parasites and the Effert of 
the Migration of the Parasites of Tertian Malarial Infection. 
Jour. Exper. Med., 1914, XIX, 523. 

Rowley-Lawson, M.: Adult Tertian Malarial Parasites Attachei' 
to Peripheral Corpuscular Mounds. The Extracellular Relation 
of the Parasites to the Red Corpuscles. Jour. Exper. Med, 191-i. 
XXI, 584. 

Schaudinn, F.: Generations- und Wirtswechsel bfl Trypano- 
soma und Siuroeliiite. Arb. a. d. kais. Gesviiulheitsainte, 1904. XX. 
387. 

Schilling. Claus: Immunitiit bei Protozoeninfektionen. Hand- 
buch d. path. Mikroorg., Kiille u. Wassermann, Zweite Auflage, 
191:;, VII. 5fi5. 



March, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



67 



Sergent, Edm. et Et.: Hemamibes des oiseaux et moustiques. 
"Generations alternates" de Schaudinn. C. r. Soc. de biol., 
Paris, 1905, LVIII, 57. 

Sergent, Edm. et Et.: Sur le second liote de I'Hfemoproteus 
(nalteridium) du pigeon. C. R. Soc. de Biol., Paris, 1906, LXI, 
494. 

Wasielewski, Tli. v.: Ueber die Verbreitung und kunstliche 
Uebertragung der Vogelmalaria. Arcli. f. Hygiene, 1901, XLI, 6S. 

Woodruff, L. L., and Erdmann, R.: Complete Periodic Nuclear 
Reorganization without Cell Fusion In a Pedigreed Race of 
Paramoeeium. Proc. Soc. Exp. Biol. & Med., N. Y., 1913-1914, XI, 
73. 

DISCUSSION 

Dr. MacCallilai.— I want to congratulate Colonel Whitmore 
upon this splendid paper which puts the whole thing in a much 
clearer light than it was before. There were two or three points 
that struck me particularly. One was the reference to the ques- 
tion as to whether the parasites are intracellular or not. I am 
sure there is no possible doubt about that. You can see them 
inside the corpuscles, see them move Inside the corpuscles, see 
them move the nucleus and see the corpuscle break and the para- 
site come out, sometimes dragging the nucleus out. 

The question of relapse is a most important one. I gathered 
from Colonel Whitmore's paper that it is his opinion that the 
asexual cycle is the thing that is responsible for the relapse. 
Colonel Whitmore's statement about the inability of these organ- 
isms to superimpose themselves on an old infection is especially 
interesting. Does that mean that no amount of introduction of 
new parasites, even of the same character, in case resistance is 
lowered, will "take" in such a person? In that case it is inter- 
esting to consider what has happened in those persons who die 
of an acute attack of malaria. You almost invariably And there 
are signs of long continued infection. Are we to understand that 
in those cases there has been one infection from the very begin- 
ning, and that they died from an acute attack merely because 
through some indiscretion they have lowered their resistance and 
have become subject to an exacerbation of their original infec- 
tion? If that is so, it would mean, I suppose, that a person can 
have only one infection, in fact is practically immune then except 
for his original malaria. 

I might say a word about the existence of malaria in some of 
the countries I visited last year. It is the disease in those tropical 
countries, especially in the East Indies. I think that cholera, 
plague and leprosy sink into insignificance compared with 
malaria. In the Malay States, for example, I found that the 
coolie laborers died off at an astounding rate. The engineer of 
public works at Kuala Lumpur told me he was in the habit of 
hiring 100 coolies at a time, different kinds each time. For 
instance, he would start with 100 Chinese coolies; 85 per cent 



would died off in a few days' time and the rest would run away. 
He would then try Malays and so on, but 95 per cent was the 
average of deaths. I did autopsies in Singapore for about 17 days 
and in that time I had 11 cases of fatal malaria at autopsy. In all 
my previous life I had seen only four fatal cases. These 11 cases 
were chiefly of the aestivo-autumnal, or subtertian type, as the 
English call them. The material, microscopically, proved to be 
most interesting. They were apparently cases of massive infec- 
tion. The intestinal mucosa showed the capillaries completely • 
plugged with organisms. In the brain also the capillaries were 
found to be completely plugged with parasites. I suppose that 
was largely responsible tor the coma in wliicli these patients were 
plunged toward the end. 

LiEUT.-CoLO.NEL Whit.moue. — 1 was very glad to hear Dr. Mac- 
Callum express himself so definitely that tlie parasite is intra- 
corpuscular. That is an important thing for our argument. 

The question of superinfection seems to be rather a broad one. 
The idea seems to be that the body has developed antibodies, and 
only certain of the parasites have become resistant; and they are 
able to live and complete their cycle just balanced by the anti- 
bodies; that is, we have a labile infection. Wasielewski was not 
able to say definitely in three of his birds whether the parasites 
circulating in the blood might have been the ones he Injected. It 
is generally considered that in the protozoa, superinfection is not 
possible so long as infection lasts. 

The question whether a man can have malaria more than once 
in his life is not so easy. Koch applied his immunity idea to 
human malaria and considered that in malarial districts the 
children who had the disease become immune, and for that reason 
we did not have malaria in adults. I think it is definitely agreed 
now that that is not the case; but that in those people who have 
had malaria as children, chronic malaria persists and that is why 
they do not have malaria as adults. They have a chronic (or 
labile) infection and are resistant to superinfection. 

I would hate to feel, however, that with all of our treatment we 
do not cure any cases of malaria. Moldovan showed that occa- 
sionally birds recover. Of course, we have followed Proteosoma in 
birds for only 29 months, and that is not a very long time in the 
life of a man. Whether a man may be infected for a few years, 
and then recover, is pretty hard to say. In malarial jlistricts, a 
great many people seem to recover, but apparently many of them 
remain infected. If they do recover, they get another infection 
right away, and always keep one going. In one place in Colombia, 
where we had occasion to go to look into some supposed yellow 
fever, it happened to be convenient to get blood from 10 persons — 
men who had not had malaria for months. In four of those 
10 we were able to find malarial parasites in the peripheral blood 
without prolonged search; so I am inclined to think that those 
people have an infection almost constantly. 



THE PHYSICIAN'S APHORISMS: 

By Hakrt 

Hippocrates was greatly revered during the middle ages by 
the Jews. He was called the " Chief of Physicians " by Mai- 
niunides and he was spoken of as "The Saint" (He-Hasid). 
His \Yorks were variously put into Hebrew from Arabic or 
from Latin translations and they were provided with Hebrew 
comnientariiis.' It is an indication of their popularity that a 



A MEDIiEVAL HEBREW SATIRE 

Friedenwald 

Hebrew satire was written in the form of the aphorisms under 
the title " The Physician's Aphorisms." 

The author was En Maimon Galipapa,' a Proveugal, of 

' whom nothing is known but that he wrote satires (probably 

in the latter^art of the 13th century), the one just mentioned 

and " A Widow's Yow," and " The Contentions of a Wife." 



' See Steinschneider, Hebraeische Uebersetzungen, Berlin, 1893. 
p. 688. 



= Concerning authorship, etc., see Davidson, Sefer Shaashuim, 
p. 119. 



68 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 325 



These works have been edited aud published under the title 
" Three Satires " by Prof. Israel Davidson (New York, 1904), 
from " a unique copy in the Bodleian Library at Oxford." 

Following the form of the Hebrew translation of Hippoc- 
rates, in which each chapter opens with the " Amar Abucrat " 
{i. e., "Hippocrates says"), each paragraph of the satire be- 
gins with the words " Amar oyeb " (■(. c, the " Enemy says " ) . 
The Hebrew style is that much in favor at that period — the use 
of Biblical expressions and phrases woven together. 

In the translation ' which follows there is no attempt to 
indicate the Bihliial references excepting in the first para- 
graph. 

The Piiysiciax's Apitoiiisiis 

Oyeli (the enemy) said: "I will pursue iind nvfrtake [Ex. 
XV, yj the worthless physicians [Zacli. XI, ll "worthless 
shepherds"]; they rejoice with the joy of harvest (Isaiah 
IX, 3) and as one gayly tripping to the music of the flute 
(Isaiah XXX, 29), when they slay a man before his tinif 
(Job XV, 32) and he is cut off from his people (Leviticus 
XVII, 4) and his place knows him no more (Psalm CIII, Ki). 
I will tell of their wicked ways, their evil shall be disclosed, 
they wlu) bring misfortune upon misfortune (Joli X\'l. 14), 
tlicy wbii arc currupting the world (I Samuel VI. .')). I will 
(•(iiiccal my name, lest they should curse me, lest in a short 
while they should stone me (Exod. XVII, 4). 

" Whoever reads one chapter of this every day will abide 
in safety, and without fear; he will find repose for himself 
when his head aches; and if he knows it by heart, it will be a 
cure for all his tlesh." 

CIIAVTEE I. GATE OF VANITY 

1. Oyel) said: ''Life is vanity; labor is regarded willi dis- 
favor; they who should work, shirk; and time jiresses.' Prac- 
tice distresses; the sick are foolish and put their trust in a 
physician, a heretic or an atheist ; those tliat aid him are stupid, 
leaning toward crooked ways. There is a time for life and for 
death, l'(ir cure iir fur the shadow of death. There is no con- 
trolling (iod's acticiu! Who will he rejected? Who will be 
spared?" 

".'. Oyeli said: " \\4ien one is ill let liim not seek the pliy- 
siciiiii ; wlietlier lie he strong oi- weak, do not desire his remedies. 
A\(iid his paths, he careful lest he ^isit you, for one dare not 
expect a miracle, lie comes M'ith haughtiness and arrogance 
in (ii'dcr to increase the trouble. \\'oe unto the |)atient with 
whom the physician comes in contact, for seven ahoininatimis 



' I desire to express my gratitude to Professor Davidson for his 
advice and his revision of tliis translation, as also to Dr. K. N. 
Rablnowitz, Dr. L. M. Palitz, and Dr. David Hlondhcini for their 
help. 

'Compare with the words of Hippocrates' Aphorisms: Life is 
short and art is long; the occasion fleeting, experience fallacious, 
and judgment difBcult. Compare likewise witli " Sayings of the 
Fathers" (II, 20) The day is sliort, tlic work is great, the 
laborers are sluggish, etc. 



are in his heart. He winks, he gestures with his fingers ; to 
increase his fee is his only thought." 

3. Oyeb said : " The foundation of medicine was brilliant 
wisdom and its ways were upright. Eecently, however, ri«\v 
people have come; the present doctors, who have learned little, 
boast : ' We are wise and know all the secrets of science.' but 
they are ignorant and empty-headed. They only take the gold 
the silver, the coin. They corrupt and do evil, but how to do 
good they know not." 

4. Oyeb said: " At the first visit of the phj'sician he says: 
' Wliy are you lying down ? Arise if v'ou wish that your illness 
and your aching shall pass away; avoid wine and lust; likewise 
eat no meat, and subdue the desire of your stomach; eat 
nothing but barley food, which is healthy for asses, or a little 
bread with lentils and .soup.' So spoke the physicians who 
were gathered in Bene Berak, that the fever might vanish. 
But the fever increases with pain, like a blossoming flower. 
The ijhysician will promise to cure, but there is no assurance." 

5. Oyeb said : " The doctor makes great pretense; he draws 
the patient's arms once to the left and then to the right ; he says 
to the pulse, that it is good, but he is as a blind man who gropes 
about at midday. Once he will say that the patient is leaping 
over mountains, then that he is walking in the plains [t. c, he is 
constantly contradicting himself] ; there is no truth in hi§ 
words; he is not able to distinguish his right hand from his 
left ! " 

G. Oyeb said : " Coiu'crning the color of the patient's urine, 
the fool will speak deception and falsehood and will tell many 
lies. He will a.sk to look at the color, to determine whether the 
sickness is in the body or in the bones, for ' his waters deceive 
not' [Isaiah LVIIL 11 |. lie shakes the urinal; he .<ees 
whether the sediment is above or at the bottom, and whether it 
is red. When its appearance is red, he will sentence to death ; 
he will look at it with sadness. But if it is white and cloudy, 
he will likewise say there is no hope. He sees but darkness and 
chaos." 

(11 M-LEi; II. A GATE OF raDICULE 

1. ( )veh said : '■ There arc four kinds of humors ° which are 
the fciiuidation of the man's constitution, to enable him to 
walk ahroad with his stafl' (Ex. XXI, 19). The temperaments 
produced liy these humors arc eight, good and bad. Each of 
the.se is opposed to the other. If there is peace among them, 
the body is healthy, there is no need for the doctor, for drugs 
nor for remedies. But when one property rises against the 
other, then tlie jicrson takes to his bed and his visage is 
marred." 

2. Oyeb said: "There are three kinds of fevers; in th*^ 
humors, in the limbs, and in the spirits, and from these the 
fever siircads either for life or death ; likewise all dise«se and 
])ain, whether cold or hot. arise from these. But 't is not 
worth while to call the doctor to aid. for he will s.'iy to liimself : 



'The four elomentary juices in Hippocrates' medicine were 
blood, phlegm, yellow bile and black bile. 



Mahch. 1018 I 



JOHNS HOPKINS HOSPITAL BULLETIN 



69 



' I shall become renowned if the patient's life is saved ; ' yet he 
is ignorant and willing to do a wrong." 

3. Oyeb said : " In a continuous or daily fever, all that the 
physician does is falsehood and pretense and in tertian and 
qnartan and complicated fevers [he is guilty of] thousands 
and myriads of errors. But what does it matter to the phy- 
sician whether the patient dies or lives, so long as he gets his 
fee; and the result of his work, let it be what it may."' 

4. Oyeb said : When one is very constipated, the physirian 
puts a syringe in the rectum, and gives an injection without 
rule or measure, in order to separate the ' bitter waters ' and 
the freces ; while the syringe is still in place, the doctor thrusts 
it further in ; the patient cries aloud and cannot endure it, but 
the doctor says: 'Keep quiet, until the mass is out. Wliy 
shall j'ou remain constipated? Wherefore shall you die before 
your time ? Now you will be clean of all impurity, and you will 
sit in cleanliness in your house. Wherefore shall you remember 
the day of your going out [i. e., your movement] .' " 

■"). Oyeb said: " When one has diarrhoea, is coueliing down 
. . . . cannot find rest for himself, and he needs to go abroad; 
when cramps, pain and suffering come on, and he is afflicted 
with his excrement and his intestines are boiling and he fills 
one vessel after another, until his abdomen and flanks cleave 
to one another ; then the physician comes, haughty and work- 
ing wonders, and he says: ' To death with the movements of 
the bowels, for I will give a remedy and this will stop ; then will 
[you] again become firm and harder than a rock.' But to the 
patient this is of no avail, as the everlasting running still con- 
tinues. Then will he cry : ' Why does this one [doctor] come 
to increase my troubles; for he has not closed the doors of my 
belly?'" 

G. Oyeb said : " When the head aches, and the pain is severe 
and the only thing is to lie abed and the patient cries : ' My 
head, my head, call the doctor, tell him about me; because of 
the headache, I am not able to taste and touch anything ; there 
is darkness [about me] and no light ! Oh, that some one might 
cast me into a pit or into the river, for it were better for me 
to die than to live; there is no hope for my desires! ' And 
behold, there come two asses, two physicians, ignorant of most 
things. One puts his hand on the patient's forehead, and the 
other on the back of his head, and they cause the patient to 
become more frightened. One says this, the other says that ; 
and the patient continues his wailing. Then they will say: 
' We need our books to find a remedy for you, that you shall 
again be able to raise your head ! ' One anoints him with the oil 
of falsehood, the other gives him ' bitter waters ' to drink ; they 
will not rest until they lower him into the pit of hell and 
uproot him completely." 

7. 0}'eb said : " When one has earache, the physician will 
examine ; then he will say that this is the illness ; why should he 
lie? He stretches forth his hand to take his fee and place it in 
his pocket or his purse. Then he prepares his remedies one by 
one, with his instruments, ointments, and wicks ; in case these 
do no good [for they are useless], he complains that it is the 



patient's fault, ' who did not hearken to my voice and did not 
incline his ear to me.' Then the patient will reply: ' Behold, I 
remembered you when I was on my couch, and I obeyed you; 
and now you stumble over your own words according to which 
the remedy was ordered; and besides you have made me 
deaf.' " 

8. Oyeb said : " When one has a spot or a cloudiness cover- 
ing the eye or is blind, and ' Jericho was straightly shut up ' 
[Joshua VI, 1, i. e., the eye is tightly closed] and the doctor 
is consulted about the disease, he answers with pride and 
arrogance : ' Who is wise and able to explain this, and who, 
like me, in past or future, can interpret it? For those who 
suffer with their eyes, my knowledge reaches to the heavens, 
and for'all humankind have I established my covenant, ily 
wisdom is greater than that of the angels; when the sight 
becomes dim, I do wondrous work to clear it ; I bring healing 
to the eye.' The patient's relatives honor him, they almost 
carry him on their hands. He visits with words of flattery 
and sits at the entrance of the house ; he prepares in his hand 
the salt of Sodom and the poison of a serpent, thorns and 
thistles, makes a plaster of them and puts it on the eye ; but 
this is as a sword and a spear, and the pain increases exceed- 
ingly and the patient cries bitterly, for his eye is blinded ! " 

CHAPTKK hi: l-IilVOLITY 

1. t)yeb said: " Concerning' fevers in the humors, the \)h\- 
sician will tell wonderful things to deceive people. He will 
proclaim all over the world, even to the islands: 'Whoever 
wishes to live, let him come unto me and I will give the right 
treatment; it has been prepared and and kept since the daj-s 
before Ashmedai, the king of the demons. Hearken to me, 
Nations, go and eat early in the morning and taste my bread 
[remedies] ; it is valued as a food for great and mighty kings ; 
the onion and the garlic mixed with straw, to be eaten in 
abundance with dry bread. Likewise, at midday and in .the 
evening, you shall eat the meat of abominable, creeping ani- 
mals, poultry or eggs. And likewise shall ye lie with women 
on a full stomach ; this is a secret remedy and cure. This ye 
shall do and live from day to day and God will be with you, 
and He will not permit the destroyer to come into your houses. 
And whoever does not believe this, will do the opposite — 
" A man's folly will pervert his path." When it is rumored 
that the plague has begun to spread, we will send people to 
Gilead to seek for remedies, or for wine and beer in the cave 
of the two daughters of Lot, for their wine is from the vineyard 
of Sodom and from the fields of Gomorrah; a remedy is near 
at hand whose virtue and value no one can estimate. But if 
one's bad luck causes him to die, you need not weep, neither 
shall you pity him.' " 

2. Oyeb said : " In liver or heart or lung diseases, the phy- 
sician will say : ' I am an expert in their treatment, and I have 
acquired much wisdom and knowledge; this is known over all 
the world.' But in truth he is like an ass under a pack-saddle 
when he opens his mouth with words of frivolity. Instead of 



^0 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 325 



\\-isdom they are [words of] stupidity and foolishness, and thus 
he says : ' For understanding of the liver, I surpass in knowledge 
and for heart disease there is no one like me except a dog: 
concerning diseases of the lung, who but I is sure that he knows 
of a wonderful cure ? And on your giving me a trial, what will 
you find but that all the seven sciences are possessed by me ? " 
And in truth, seven are the abominations in 'his heart and 
he has no conscience within him. Verily, while he continues 
in his self-flattery, the patient is in a critical condition : and 
though they find him to be ignorant, and put him to shame, yet 
will he not cease from his evil actions." 

3. Oyeb said: " Go and see the doings of the physician and 
his remedies, for which he carries his sheaves [t. e., fees]. He 
opens his mouth without limit, asserting that he knows all 
about diseases, accidents and their causes ; he talks much about 
how to prepare aid and remedy. He goes to the druggist with 
pride, raises his hand to write, in order to show his ring. He 
prescribes in a foreign language, for his science is foreign to 
him ; [he does this] in order to remove the crop with its 
feathers [in order to " bleed " the jjatient] ; and between one 
word and the other he spits; this is his manner and habit. In 
unimportant matters he makes himself very busy. He says to 
the druggist: ' Take the liquid to the patient, charge him as 
much as you can, and ask for the pay, ere his lamp will be 
extinguished. And if he finds in it trouble and misery, we are 
innocent, since " all who .spoil fire exempted." ' ° Both rejoice 
in their prey, as people who have done charity. And what 
does it matter to them if the patient dies, for the earth will 
cover him! 'And what does it matter to us? We shall li\e 
on ! ' " 

1. Oyeb said: "Listen, all ye people, to the words of the 
stupid quack who dwells in aristocratic places, when he says: 
' I am descended from ancient kings, I am the son of sages, 
since the day that God created man. Who has secured even 
half of my knowledge in understanding the secrets of herbs, 
and of difl'erent drugs? Who knows their many high and low 
degrees ? I know each one according to its name and place.' 

" About bloodletting he will say: ' Did not my mind do all 
this ? For I understand how to distinguish between good and 
bad hours and lucky and unlucky moments.' But he does not 
even know when it is new moon nor when it is full moon ; ho 
claims to know the days of bad omen, and that the day on which 
Haman was hanged is dangerous for bloodletting, unless it be 
for circumcision." 

5. Oyeb said : " What a crime it is for the physician to 
speak foolishness in his ignorance and to extol himself with 
much wisdom. Woe unto such a shame! Woe unto such a 
disgrace! Even when one asks him about the limitations of 
medicine, he will answer arrogantly: ' Is any knowledge hid- 
den from me ? What sort of a question is this ? There are two 
limits, you see, a limit on one side and a limit on the other 
side ! ' And if he is asked about fever, he will answer that this 



" A Mishnalc law that exempts destruction of an object on the 
Sabbath from the penalty imposed for worlv done. 



is a burning without fuel, coming hurriedly at different times 
one after the other. He will declare that the law [governing 
the fever] is hidden with the Lord ; no man will ever know it. 
Concerning the beginning of the disease, its progress and 
disappearance, who can understand its nature and its duration 
and its end ; all his words are void and vanity." 

6. Oyeb said : " A physician's mistake leads to crime, quar- 
rels and disputes. Of the dead he says that he is alive, and 
of the living that he is dead ; there is no truth in his speech. 
He is the Reaper's agent; he is the assistant of the Angel of 
Death and his messenger; this is his function. He gathere 
medical books new and old and of many kinds to make a show 
of them, but not to read them. And if there are errors in them, 
he does not discover them ; they remain where they are, there is 
no one to correct them. If he is asked about a chapter or a 
good treatise, he will put off the answer for the morrow, and at 
an opportune time he will say : ' Go away, go home, do you 
wish to examine me? Shall such a man as I answer fools? 
I am the physician who cures all maladies ! ' " 

'i'. Oyeb said : " This is the way the present doctors slaugh- 
ter, in order to get large fees and to be regarded as experienced. 
For the instructors announce : ' Whoever practices medicine 
without getting fees deserves to be stoned. Learn to make 
money by analog}' from the Field of Ephron, [as Ephron, the 
son of Zohar, took from Abraham 400 silver shekalim to bury 
Sarah] ; thus you will reap benefit and save. Go ahead and 
take for yourself, slaughter j'our sacrifice, and so eat [your 
fill] . Be ready to visit the patients, but not for mere talk or 
to be their aid and jirotector; for large compensation only 
and not for nothing! Here you have an example: King 
Hezekiah hid the book of medicine, because "the physician did 
not get the reward of his labor. They would put off payment 
saying: 'Wait until Shiloh (Messiah) comes; go home in 
peace, but dare not to come here to ask for your reward.' 
Therefore, be careful in your practice, and do not come to the 
patient's house until you get your heave offering; and do not 
leave the house with empty hands, or with only some eggs 
or a piece of bread.' " 

ClI.a-TER IV. DECEIT 

L Oycli said: "Xow let us describe all the remedies and 
their order, which were established in the days of Terah 
[father of Abraham] in Haran. A liquid medicine for fevers, 
and it is like sharp swords. Let there be taken roots of broom- 
bush and grass of nets, and the flowers of priesthood, from 
each one a part; a withered leaf and a leaf of thought, from 
each one an ounce or a pound; the shell of garlic, beans of 
the garden, a rod and a bullrush and foam also, from each 
one and a half pint, filled or empty ; wasp's honey and the bray- 
ing of an ass, and the threads of net; the mucus of the nose, 
the noise of millstones, from each one a handful; all this ])ut 
in a pot, perforated or broken; let it be cooked with cursed 
water on the fire of hell [you can obtain it gratis] until it has 
boiled down one-half, and then it will be ready to drink. One 
bowl of foam and a pitcher of water lot him drink at twilight. 



JlAIiCH, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



ri 



and let [the sick] taste of it at dawn. This cup of swords will 
empty him, without leaving a remnant until the intestines drop 
out; and, when he looks at the cup, his abdomen will swell. 

2. " Another general remedy for all diseases: Let there be 
taken the mouth of a serpent, the noise of a storm, the black- 
ness of the Ethiopian, the whiteness of women, oil of quarrel 
and contention, from each one-half measure ; the tail of a 
lizard, the twittering of birds, the base of a camel's hump, the 
wings of flies, and the brain of a flea, and a whole fat tail, and 
the blossoms of shame and reproach ; this you must cook ; boil 
it in presumptuous water, with the eggs of lice, from each two 
kinds, in a boiling kettle full of crushed things and it shall 
be kept boiling until the water turns to vapor; let [the sick] 
drink it in the evening, morning and noon, and whether 
he will iind a cure for his malady in the end will show, espe- 
cially after his death." 

;i. Oyeb said : " This prescription will help in every fever, 
also in any illness or abscess : Take pure frankincense and 
powdered dust, thorns, soot of a furnace, and much smoke, 
from each one an equal measure with menstrual blood and the 
liquid part of faeces and thin dirt and fffices of wild foxes, from 
each one five shekels ; oil of hypocrisy, and shame and reproach, 
and bitter spices, from each one a manah ; perforated baskets, 
deadly venom of a poisoning snake, semen of evil doers, 
occipita of frogs, cow's dung and deadly flies, juice of brook- 
stones, and soup of putrid flesh, of each one an equal weight ; 
after the art of the apothecary shall they be mixed. All who 
eat it will do evil and will become heart-sick when they 
take it." 

4. Oyeb said: "In tlic valley of weeping on the night of 
the Ninth of Ab, when the lamentations are being read, the 
doctors of the present day prepare the oil, to anoint the heads 
of the Am ha-Aretz [ignoramus] so they can fleece them : 
First take salt of Sodom, falsehood and deceit, poison of ser- 
pents and the head of an asp, and the water of those who have 



to bring offerings for transgression ; nets and thorns of vine- 
yards, and powdered dry grass, oil of burning, sweat of a tired 
person, from each one a tenth of an ephah. Together with 
all these, pound the wicked fool in a mortar, with crookedness ; 
and this shall be the ointment. Whoever is rubbed with this 
will have sorrow and groaning instead of joy; he vrill have 
sickness instead of gladness, he will hope for cure, but, behold, 
there will be terror. 

"This was written and signed by the scribe of the city; all 
of it by his strength and of his might ; who can bear it, for 
it will be as a stumbling-stone ? With it he will dig for himself 
his own deep grave." 

CIIAPTEi; V. PE.iCE 

1. Oheb [the friend] said : " Now I repent, if I have spoken 
badly about the physicians, for I meant well ! To wake their 
conscience; to make them study better their medical books 
[is my sole purpose]. Let them but be correct in their work 
and strong. Let them not waste their days in vanity and 
deceit. Let them walk before the people with courage; from 
this day on there shall be peace [between us]. I will tell no 
more of their shortcomings. From having been their foe, I will 
again become their friend ; it is I who am speaking to them ! " 

2. Oheb said : " We are tired of many words. Let us make 
peace between us and become friends. If I have spoken till 
now because of my sorrow and anger, let friendshij) return 
and I myself shall lead it. If I have spoken too much, all will 
again be good and calm like the waters of Pishon. And you 
physicians, do your work diligently and with clean hands : 
and take for yourselves silver or gold, for the living must die 
and the dead will be restored to life. Seize fortune when it 
deals pleasantly with people. I have found a noted proverb, 
and it shall be as a sign to you : ' Good fortune comes not to the 
faithful man.' " 



MINUTE ON THE DEATH OF DR. THP]ODORE C. JANEWAY 

ADOPTED BY THE MEDICAL BOARD OF THE JOHNS HOPKINS HOSPITAL OF MONDAY, JANUARY 7, 1918, AND 

PRESENTED TO THE BOARD OF TRUSTEES 



It is with a sense of sorrow and of personal loss that the 
Medical Board of The Johns Hopkins Hospital record the 
death of Theodore Caldwell Janeway, for a little more than 
three years the physician-in-chief to the hospital. 

Dr. Janeway was a marked man from the beginning of his 
medical, career. He was a lecturer in medicine first at the 
Bellevue Medical College and later at Columbia University 
where, in 1909, he was chosen Bard professor of medicine. He 
was at dilferent times visiting physician to the City Hospital, 
St. Luke's Hospital and the Presbyterian Hospital in New 
York. In 1911, he was called to Baltimore to become pro- 
fessor of medicine in the university and chief of the medical 
clinic. In these positions he served until his death. Born on 



November 2. 1872, he died of pneumonia on December 27. 
1917, at the early age of 45. 

His natural medical ability he inherited as the son of a dis- 
tinguished physician, but he acquired also from long and 
sympathetic association with his father a passion for medicine 
as an intellectual pursuit and an appreciation of it as a means 
of benefiting and assisting his fellow man. He was thus 
peculiarly fitted to serve as the head of a medical clinic, for to 
his great medical skill and judgment was added deep sympathy 
for sufl^ering humanity. 

The knowledge of medicine brought to him a sense of 
responsibility which was not to be satisfied solely by the treat- 
ment of patients under his care in the hos])ital or dispensary. 



JOHNS HOPKIXS HOSPITAL BULLETIN 



[No. 325 



He keenly felt the economic and physical distress so frequently 
associated with and resulting from disease, and he gave to 
many charitable associations freely of his time and advice 
ill the at(cin])t to improve the condition of the iinrdrtunatc. 
lie worked tirelessly and without regard fur his iicalth or 
slrcnu-tli. 

A natural tcaciicr. a clear, forceful exi)ositor and an pn- 
tiiusiast that others should recognize the possibilities of 
medical science as well as the duties and obligations resting 
upon those skilled in medicine, he exerted a profound influ- 



ence upon his students and associates and an influence that 
will not cease with his death. 

Called into the service of the government in the spring of 
1917, Dr. Janeway gave to the surgeon generaFs office his 
untiring efforts as befitted one with the high sense of patriot- 
ism that characterized him. The love of country led him to 
spend himself freely and to such an extent that he could not 
withstand the disease to which lie fell a victim, young in years 
but having by precept and example influenced much the lives 
of many men. 



PROCEEDINGS OF SOCIETIES 



THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY 

OCTOBER :ri. I'.m 

1. Personal Observations of the Hopkins Unit in France. Jay 

McLea.n'. 

2. Extracts from Letters from Various IVlembers of the Hopkins 

Unit. 

NOVEMBER .(. /.''/7 

1. Adenoma of the Recto-Vaginal Septum. Dh. T. S. Clllex. 

Pulilisiicd ill the I')!'!,:,!"! IX. Xcjveinlier, WW,. 

2. Experiences In a Base Hospital. Dk. Thojias McCrae. 

It is always important to kee|i iii mind that no one man sees 
all pha.ses of disease in war : iiuh'cd, tlie great majority of men 
will .see only one phase. .Men in dill'ereut places see different 
stages of the same disease, rraetically all the patients in the 
base hospitals in England come from France, some only 36-J:8 
h(.nirs from the trenches. My work was in an active general 
hospital of 2080 l)(>ds, with a number of associated convalescent 
hospitals, so that the ser\ ice was constantly moving. One 
might think that to bandle a service of 1000 medical or sur- 
gical patients would be difficult, but with proper methods it 
seemed little more difficult than the management of 100 beds. 

In regard to the transport of the wounded, a message would 
come, for exani])lc, that ISO stretcher cases or 100 walking 
cases were on tht^ way. The message wouhl be received some 
hours ahead, and the coinny trains wouhl come within five 
minutes of the specified time. The iiospital trains are very 
well equipped, and the man in charge slojis the train, when 
lie wishes, for emergency cases. When the trains arri\eil. the 
stretchers were ready and the cases were a.ssigned to the wards 
on the station platform. Every wounded patient carried on 
his coat a thick envelfi]ie of waterproof paper, on the outside of 
which was the diaunosis. There was enough on the card to 
indicate where the man helonge(l. Tlie adjutant would look 
at till' caril and \\riti> on it the ward to which the man was 
assigned. The a\eragc time for a coiuov of 120 st retcher cases 
was one JKnir from the time the train was in to ilie time the 
last man was in bed. 

Among the clisea.ses peculiar to war. we may lirst mention 
trench fever. This is absolutely new, so far as I could sec. 
'J'he vast majority of the cases come from the trenches, but a 
certain number ba\e arisen back of the trenches. Statements 



are made that the disease has originated in hospitals in Eng- 
land among nurses and orderlies waiting on patients with the 
disease. I was told one case occurred iu a nurse in the hos- 
jiital where 1 was. I was able to prove that this was not so, 
and I could not find any one who had definitely seen such a 
case. The jiatients have an on.set much like any other acute 
febrile di.sease. They feel badly for a day or two, have a good 
deal of headache, malaise, chills, fever and loss of appetite. 
The fever begins comparatively early and is not necessarily 
high. When those symptoms develop at the front, the men are 
sent down at once, and I saw some of them in about three or 
four days after the onset. In general, there is nothing par- 
ticular in the examination, except one striking thing. They 
complain of pain, which is generally described as being in the 
shins. The fever is variable; it lasts sometimes five, six or 
seven days, sometimes only three or four, and then drops and 
the temperature runs along for some days at normal. After 
this interval of from 5-7 days, there is a sudden elevation in 
temperature, the fever going up to 102°-104°. Tliis persists for 
24 hours and then drops to normal. There is another afebrile 
period for 5-7 days, and then another paroxysm, the tempera- 
ture again dropjiiug to normal. That may go on for seven or 
eight attacks. The majority of the patients had two or three : 
after that the tem]ieraturc was normal and there was no return 
of fever. With this elevation of temperature, there is ap]iar- 
ently no increase in leucocytes. The pulse always goes u|i a 
little and the )>atient looks very ill. The point of jiarticular 
interest is the condition in the legs calleil " painful shin." Tn 
the majority of cases the shin is \ery tender, in some cases 
when one goes near the bed, tlu' man implores y<iu not to touch 
it, a coiulition I have only seen <itlierwise in vc>ry severe cases of 
rlu'umatic fever. If you examine more carefully, you liml that 
they often have tenderness behind the knees. Indeed, a good 
many id" the patients had as much tenderness on pressure be- 
hind the knees as in the shins. After the period of fever is 
over, there is nothing left but this excruciating pain, which is 
usually worse at night ; and it is very common to find these men 
sleeping during the day. Xatnrally. in such a condition, symp- 
tomatic therapy is of iniportancc. but it was not \ery success- 
ful. Tjocally. the a]iplication of a solution of Epsoin salts gave 
more ri'licf than anything else. I was interested in trying the 
eil'ect of sunlight. It acted like magic in some cases, but un- 



Mauch, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



fortunately they were the exceptions. Some of the patients 
were not affected at all. The views as to the etiology are con- 
flicting and not one has been confirmed. A good deal of evi- 
dence points to the fact that the disease is carried by lice. 

A second disease which one might say is peculiar to war, is 
the war nephritis, in which there certainly are seen features 
which are different from the ordinary acute nephritis seen in 
civil life. These cases usually have an acute onset. Many of 
them do not know anything is wrong until told by their com- 
rades that their faces are swollen. Some begin with severe 
headache and others have to fall out on a march on an'count of 
<lys])nea ; others feel weak and have pain throughout the 
body. In the early days edema is comparatively common, 
[larticnlarly of tlie face, and there is slight fever. ()\iv feds 
after watching these patients that such a case may go on in- 
definitely. It is called acute nephritis, but it goes on for week 
after week without any apparent change. The edema clears up 
fairly promptly. Uremia is not very common, although we had 
several patients brought in with it, who. when they left France, 
had apparently been well. After a few days, as the edema disap- 
pears, the, patients feel better except for the persistence of 
excessive headache, which is generally relieved by luml)ar 
puncture. The most persistent finding was blood in the urine, 
which went on indefinitely. It was not, as a rule, macroscopic 
after the first few days. There were a certain number of pus 
cells in nearly all these patients, and one curious thing was that 
the patients who had uremia were the ones who did the best. 
The duration in those cases was less than in the men who did 
not have nremia. The blood-pressure was not at all constant : 
in many there was a tendency to a rise during tlie day. often 
associated with the headache. 

One naturally wonders what is at the bottom of these ca.ses. 
A few are instances of an acute flare-\ip of an old nephritis, 
but these are only a small number. Again, one thinks of an 
infection from the throat. This has been studied ijretty 
thoroughly, and it cannot be found except in a very small 
proportion. Pathologically, the features are exactly like those 
found after scarlet fever. In the majority of the cases the 
etiology is unknown. 

One saw a certain numlier of cases of jaundit-e. We were 
hunting very busily for spirochetes, but did not l.ud any. A 
number of cases resembled ordinary catarrhal jaundice; others 
were much more severe and one did not know what to call them. 

One conditicm is going to worry every medical man i]) war 
si'rvicc, and that is the cases of so-called soldier's heart. I sav,- 
nothing in these cases in any way peculiar to war. They were 
what we would ordinarily term cardiac neuroses, with perhaps 
a few additional points. There are nearly always some dis- 
turbed sensations referred to the heart. The patients often 
complain of pain which is a striking feature of the cases. In 
some there is l)reathlessness on any exertion and there is gen- 
erally marked va.somotor disturbance, which is sometimes very 
striking. Examination shows very little. In a few there is 
evidence of dilatation, but in the great majority of cases you 
can find very little in the way of an actual objective sign. 



There has been a great deal of discussion as to the cause of 
this condition. No doubt nervous strain plays a tremendous 
part. Physical strain did not seem to be a contributing factor. 
Perhaps a good deal of it might be attributed to tobacco. 
Smoking is almost constant, and nearly always cigarettes. The 
average runs from 20-40 a day. It is a serious question in the 
hospitals, where tobacco is issued as food is issued. It is a 
verj- difficult matter to cut down tobacco when it is being con- 
stantly served. If one goes into the history carefully, one is 
impressed by the number who have a susceptibility to tobacco. 
Some men regard smoking as the prime factor in these dis- 
turbances of the heart. 

Of course, we looked for internal secretion di.«turbances, but 
tlicy aie nearly always conspicuous by their absence. A certain 
amount of infection may have played a part, but this is by no 
means invariable. In a few cases there had been damage to 
the heart beforelumd, but there was no one thing that stood 
out. The more you observe them, the more you feel the tre- 
mendous iniportance of the nervous disturbance. 

Of peculiar interest were the patients with gas poisoning. 
Early in the summer we got quite a number of gassed patients 
with what was designated as the " new gas." It was entirely 
different from any used before. A little later men spoke of it 
as " mustard gas." I asked many of them what they had 
noticed. Some had not noticed anything, but others said there 
was a smell of garlic. A few days later a chap came in who 
had been a chemist, and he said he was certain the smell was 
that of arsenic fumes. The men came in with varying .symp- 
toms. Wv had ten men come in together, who had been gassed 
at the same time with very different results. As a rule they 
felt nothing at the time. Sometimes there was con.*triction 
and difficulty in lireathing, but the majority did not know 
they had been gassed. Some time afterwards, in from 2-3 
hours to 2 days' time, the first symptoms appear, a profuse 
vomiting which lasts a few hours in some cases, in others for 
days. .Many had irritation of the eyes, conjunctival redness 
and swelling, marked pliotophobia and inability to use the 
eyes in a light at all bright. That lasts a varying time, some- 
times as long as 2-3 weeks. A few had corneal ulcer. In 
certjiin others, the brunt of the injury fell on the larynx. 
There were some very acute cases of laryngitis, with a good 
deal of cough, and in some patients marked bronchitis. Per- 
ha]>s the most curious sign of all was the effect on the skin in 
certain of these patients. Some of them looked as if they had 
been stripped and some one had thrown mud on them in the cen- 
ter of the chest, and from there it had spla.shcd all over them. 
There was nearly always pigmentation and of a remarkable 
appearance. Some desquamated very promptly, while others 
went on to an acute dermatitis. The Tommies called these 
lesions "gas burns." They began as a small bleb, which 
jwrhaps might increase until it was as large as the palm of 
one's hand. I saw no instance in which a soldier was ap- 
parently permanently damaged by this particular gas, although 
it is of course too early to say positively, except in some of the 
laryngeal cases. The eye conditions recovered ]ierfectly. Some 



74 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 325 



of the men developed severe attacks of abdominal pain 2-3 weeks 
after being gassed, suggesting acute appendicitis. The first 
one I saw liad rigidity, muscle spasm and great tenderness and 
it was a question whether he should be operated upon or not. 
However, the leucocytes were not increased and we waited; in 
24 hours the pain had gone. There were a number of such 
cases. 

The ueiu'ological side of the work is a subject upon which 
you might talk at great length. The two main problems are 
the injuries of the nervous system and the so-called war shock. 
Wounds of the head and nerves are simply bewildering. One 
of the great problems is as to when one should operate and 
when they should be left alone. Theoretically it may sound 
easy to decide, but it is a very difficult problem to settle. 
Among the patients with war shock some will talk frankly 
about what happened, some have no recollection at all, while 
others hesitate and you cannot get them to speak. It seems 
to me probable that in some of these shock cases there has 
been a certain amount of organic damage. One thing that 
liarms tlie war-shock patients particularly is travel. A thunder- 
storm would excite them greatly. With lightning, tliey would 
often jump off the bed. If you could let one war-shock patient 
.see another chap " acting up," he would usually siibside and 
quiet down for an hour or two. We did not get a large number 
of tliese patients, but when a lot came in, we would generally 
try to pick out the most intelligent and work the matter out 
with him. In a certain number of cases, one got marked 
results. One patient lost all outward signs in about four days. 
This created a tremendous interest in the ward. We put him 
to work with other patients and he was the means of clearing 
up a number of the men wlio had come with liim. When his 
condition had been cxplaiiu'd to him, lie said: '"Why didn't 
I know that before? 1 see the whcilc thing now. If I had 
known before 1 went up to the front. I would never have been 
like this, f went up and heard a whole lot about shell shock 
and was all ri'ady for it before it came." This particular man 
liad been liuried for a few minutes and came out with well- 
marked sh(]rk. With some cases it was impossible to do any- 
tiiing by analysis or suggestion. They have to have a certain 
amount of intelligence before one can do a great deal. 

iti.xed u]) with the whole subject of gas poisoning is aphonia. 
Many ]inticiils have difficulty with speech and a certain number 
Mi(> dclinitcdy hysterical, but I am not referring to them at 
|M-rscnt. Many patients who had been gassed, or who had had 
various disturbances, were left with aphonia. The majority 
iiii))n)\c slowly. Anotlier thing which is extremely connnon is 
stanmieriiig. A great many of tlic men stammer, not neces- 
saiily Ihr paliciits with war shock. It is striking to see how 
many in the wards are alfected. 

I mention one point because it is apju-aring quite often in the 
literature, and that is the cases with foreign bodies in the 
lungs. I am not speaking of the patients who need .«urgical 
treatment, liut of those who have recovered and who have 
foreign bodies in the lungs. As you know, the French sur- 
geons are strongly advocating operating on these jiatients. One 



hears that the mortality is rather high. The feeling in the 
Canadian service is strongly again,st operation. I saw a num- 
ber and in the great majority you could find little in the way 
of signs. It seems bad. practice to meddle with a condition 
which is not serious, at any rate at present, unless there are 
definite indications that one is going to make things better. 

With regard to tuberculosis in the soldier, my feeling is that 
you cannot keep the standards up too high. To say as some 
men have said and written, that because a patient has had 
tuberculosis and has recovered is no reason why he shoidd be 
rejected, «eems to me to be absolutely wrong ; and to say that 
men with pulmonary lesions that are not causing symptoms 
should be passed, appears to me to be abject nonsense. The man 
who has had tuberculosis should not be sent to the front line, 
although such men could be used back of the lines in many 
ways. Some writers claim that men with tuberculosis have 
done very well ; perhaps they do, but when you think of them 
being constantly damp, sleeping in dugouts crowded as closely 
as possible, and often crowded into cellars, the conditions are 
certainly bad. In addition, the men with bacteria in the sputum 
are spreading infection ; it could not be otherwise. My feeling 
is that the men who have had bronchitis or chronic emphysema 
should not go to the front lines. I do not believe that they 
should be passed as Class A men. 

The medical officers who go to the front have some nice work 
ahead of them in diagnosing tuberculosis in the soldier. It is 
an entirely dilferent matter from diagnosing tubercidosis in 
the civilian. The men have nearly all had bronchitis; they 
have nearly all lost weight. You hear that every one gains 
weight at the front; some do, but many have lost a great deal. 
With the bronchitis, they often have blood-streaked sp^itum, 
and there is also often slight fever. You get a man like that, 
particularly with signs of an old lesion at one ape.x, and what 
are you going to do about it? Many men with acute tuber- 
culosis came back from the trenches with no fevei', while the 
bronchitis patients did have fever. The X-ray plates did not 
help very much, because many patients showed marked shadows 
through the lungs. Then, again, you have not unlimited time 
to settle tlie matter; you have got to decide it promptly. As 
cue senior medical officer said: "What we want in the men 
in charge is that they make decisions promptly. The man who 
handicaps us is the man who hesitates in making decisions." 
Now, how are you going to settle promptly cases like those I 
liavo mentioned ? If the patient has tuberculosis, he ought to 
be sent home promptly ; but we do not want to send back a chap 
wlio has a lironcliitis that is going to clear up. The diagnosis 
of tuiici-culosis is one of the most dillicnlt problems they have 
over there. 

Another class of diseases is the gonorrheal infections and 
lues. The work in a war hospital gave me a big surpri.se in ref- 
erence to them. There are more patients with lues in the medi- 
cal service of hospitals in this country to-day, several times over, 
than in the general military hospital. Cases of active infection 
would not bo seen in general hospitals. However, when one 
lakes n 1000 lii'd service constantly full, one would expect a 



-MAKCir. 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



75 



considerable incidence. The only gonococcus cases were old 
infections and there were very few of those. Instances of lues 
were extremely rare. We always had a large number of Was- 
seiinann reactions done, and the amazing thing was to find 
low few were positive. Diagnoses made by tlie ^\'assernlann 
were very occasional; indeed, there was notliing like the oc- 
currence that one gets iu an ordinary civil hospital. A certain 
number of the men had been most efficiently treated and showed 
negative reactions. The army treatment for lues is very 
thorough. 

Just a note about the dental work. That was a very pleasant 
surprise. There are not many hospitals in this country to-day 
that are having anything like the grade of dental work done 
that was carried on in the military hospital to which I was at- 
tached. The whole .staff was there all the time and any doubt- 
ful cases went to the chief at once. The mouth condition in 
the soldiers was much better than one would expect it to be. 
The men were taught to take care of their mouths, and it was 
a pleasure to see the way in which the dental work was done. 

;Mentioii should be made of the orthopedic work. American 
orthopedic men are largelj' responsible for the establishment 
of orthopedic centers attached to different hospitals. One 
cannot speak too highly of the work they are doing. 

The X-ray work is a tremendous burden. The regulation is 
that any patient who may have a foreign body in him must Ijc 
X-rayed, and with one or two hundred coming in at once, you 
may imagine the strain. 

The mortality in the hospitals in England is surprisingly 
low. On the medical service where I was during the summer, 
there were four deaths, three from tuberculosis and one from 
pneumonia. There were no deaths from nephritis and none 
from gas poisoning. The deaths on the surgical side were 
also very few. 

One point that comes up constantly is that of prognosis and 
this is most difficult to handle. Here is a man who comes in, 
and the question arises, " Is he likely to be well in a month, or 
will it take three or six months, and at the end of that time 
what sort of shape will he be in ? " That problem comes up 
every day. With the Canadians, if the case was to be a long 
one, it was better to send him back to Canada. If he is going 
to get well, of how much use wiU he be ? The problems arc 
\ery nmch the same as those the American troops will have : 
and one must decide promptly as there are always patients 
waiting to come in. Another point is that it is so difficult to 
get experience. You discharge a man and send him on to a 
convalescent home and then you see no more of him. Yuu 
cannot easily get data concerning him. Deciding wisely about 
the outlook for a patient is perhaps the most difficult problem 
of all. 

The personal side is most interesting; it was a pleasure to 
spend as many hours as possible in the late afternoon and 
evening talking to the men. You could not get such a varied 
collection of men anywhere else. I often think of three adja- 
cent beds in one of the wards. In one was a Montreal bar- 
rister, a graduate of au Enslish universitv, in the next a 



typical Devonshire rustic, and in the third a Canadian Indian. 
It was impossible to get the men to talk much about what 
they had done, and not much about what they had seen. One 
of the most interesting groups came in one night, and just by 
chance about 20 beds in one ward were filled by men who had 
gone to France in August, 1914:. When you saw those men you 
realized to some extent why that original force was able to 
do what it did. It was the first time that one or two of them 
had been l)ack in three years. Y^ou could not get them to 
talk very much. They had, of course, been through all the 
terrible first days of the war. The thing that came out in 
talking with them was the fearful fatigue. As one chap put 
it : " You would get a chance to stop and you would drop there 
and feel that you could never get on your feet again. The 
whole thing now is just a blur of fatigue, beyond anything 
an3rbody could describe." Those were the chaps one felt like 
saluting for what they had done for every one of us. 

They are great readers and devour books. What impressed 
me most was the amount of serious reading many of them were 
doing ; collections of poems from many authors were extremely 
popular. It was surjjrising to find how much Shakespeare was 
read. Of course, they were not particularly keen on war 
literature. 

Tlie men are great collectors. One night when a convoy was 
coming in late, I saw the stretcher bearers having a hard time of 
it with one chap who had what appeared to be a considerable 
mass projecting on either side of the stretcher. The weight 
was so great they were obliged to put the stretcher down to 
rest. Across the foot was a great sack about 6 feet long, full 
at first sight of what appeared to be junk. The chap had col- 
lected helmets and all sorts of stuff. The wonder was how he 
ever got it through. 

The personal side of the work was intensely interesting. The 
gratitude they had for what you were doing for them made 
you ashamed : it seemed so little compared with what they had 
done. 

One important thing I would like to emphasize for the 
medical men who are going over. The first lesson a soldier 
learns is that of obedience and the second is how to wait. That 
lesson we all must learn. You cannot expect that the wounded 
and sick are going to come in at maximum all the time, al- 
though you have got to be prepared for the maximum. The 
medical organization has to be prepared for the largest pos- 
sible volume of sick and wounded that can come at any given 
time. You can only do that by having many more men than 
are necessary for the average. Of couree, the waiting is slow 
work, but it is one of the things that has to be learned. 

The thing that made tlie strongest unpression on me over 
there was the spirit of the men. I did not see the men at the 
front, but of the men iu the hospitals nothing finer than the 
patience shown can be imagined. I cannot think of any one 
working in a war hospital for even a short time without com- 
ing away with his belief in the essential soundness of human 
nature strenathened. 



76 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 325 



NOVEMBER 19, 1917 

1. Studies on Blood Sugar. Db. Louis Hamjiax and Dk. I. 

HlHSCHMAX. 

2. Blood Cultures in Miliary Tuberculosis. Dr. Mildked Clough. 
I'lilili.'^licd ill the BrLi.ETix. Decenilier. lltlT. 

3. Auscultation of the Pulmonary Apices in Young Men.' 

(Abstract.) Dk. John T. King, Jr., First Lieut., M. R. C. 

The ob,servatious reported here were made during a recent 
examination for tubereiilosis of about 22,000 troops at Chicka- 
mauga Park liy a board of tuberculosis examiners. During the 
course of the work numerous men were found to present certain 
crackling sounds during auscultation, especially in the super- 
clavicular fossffi, which so closely simulated rales, that their 
identification became the most difficult problem that had to be 
•solved. It was of importance to identify such sounds, because 
the board was authorized to disqualify any soldier who showed 
persistent moist rales in the upper lobes. During the latter part 
of the work the writer noted the frequency of adventitious 
sounds ill the upper lobes in the examination of 819 men. 

ill 1 per cent of men examined crepitations were heard at or 
near one or more joints: the joints especially noted were tlie 
.scapular, costo-sternal, and .<terno-clavicular articulations and 
the shoulders anteriorly. 

In 2.8 per cent certain crackles, usually rather loiul and 
explosive, were heard for one or more respirations at the apices, 
disappearing promptly during continued breathing. 

In 2.07 i^er cent were found the persistent apical clicks or 
crackles of the type that had proved so confusing. 

No description of tlie last-named group of adventitious 
sounds was found in tjic usual text-books on thoracic diagnosis. 
Itiishncil refers to a brief descri|)tion (if such crackles noted 
by IJoseiibach over 10 years ngo. lie found them must uftcu 
in muscular young men and diildren. 



' Published in The Military Surgeon, January, 1918. 



Joint crepitations may often be recognized by their groan- 
ing or grating quality. Confusing scapular sounds may be 
eliminated by one of three procedures: (1) By having the 
subject fold his arms and grasp the opposite shoulders with 
his hands; (2) by having him, while standing, bend the trunk 
forward to a horizontal position and allow the arms to hang 
limply downward; (3) by having him grasp an object at a 
level about as high as he can reach and exert enough weight 
on his arms to fix the scapulae apart. Crepitations from the 
lateral sternal articulations may often be eliminated by having 
the subject throw his shoulders as far backward as possible. 

Transient apical crackles, originating probably in the neck 
muscles, are often easily recognized by a loud, explosive quality. 
They are seldom reproduced by coughing. 

The persistent ajjical crackles in healthy men are more diffi- 
cult to distinguish from true rales than are any other adven- 
titious sounds in the upper lobes. They are of every size, and 
occur singly or in sequence. Single clicks are usually of 
this type. All such crackles are most often heard when the 
subject holds his head in the position customary during exam- 
inations — slightly averted from the ai>ex under examination. 
Such sounds often disappear if tlic chin is placed high in the 
air or if it is turned slightly toward the side that is being ex- 
amined. These crackles are .seldom increased by coughing, and 
usually occur during inspiration, but may be present in both 
phases of respiration. They are usually more intense when the 
stethoscope is directed medially, toward the neck muscles. 
Eosenbach reproduced such sounds by moving the neck muscles 
while the subject held his lireath. .Ajoical crackles of the above 
types almost certainly originate in the neck muscles and are 
of significance only in being dilVcrcntiated from intra- 
pulmonary rales. 

NOVEMBER ^3, 19n 
On Two Fronts. Dr. Wilfred T. Grenfell. 



BOOKS RECEIVED 



A Treatise on Regional Suryeri/. By Various Authors. Edited by 
John Fairbairn Binnie, A. M., C. M., F. A. C. S. Vol. I. With 
351 illustrations. 1917. S°. 652 pages. P. Blakistons Son 
& Co., Philadelphia. 

Saint Bartholomew's Hospitdl Reports. ICdited by F. \V. Andrews, 
W. McAdam Eccles, G. E. Cask, W. D. Harmer, H. Thursfield, 
H. Williamson. Volumes L and LIl, 1914 and 1916. 8". 
244 pages, 167 pages. Smith, Elder & Co.; John Murray. 
London. 

Obstetrics. A Text-book for tlie Use of Students and Practitioners. 
By J. Whitridge Williams. Fourth enlarged and revised edi- 
tion. 1917. S°. 1029 pages. 1). Appleton & Co., New York and 
London. 



Carnegie Endoioiienl for International Peaee. Founded Decem- 
ber 14, 1910. Year Book for 1917. No. 6. 1917. S°. 213 pages. 
Wasliington, D. C. 

The Rockefeller Foundation, International Health Board. Third 
Annual Report, January 1, 1916-December 31, 1916. 1917. 8°. 
246 pages. New York City. 

State of Iowa. Board of Control of slate Institutions. Tenth Bien- 
nial Report for the period ending June 30, 1916. 11917.) 
8°. 405 pages. Des Moines, Iowa. 

Surgical Therai)ciitics and Operative Technique. By E. Doyen. 
English edition prepared by the author in collaboration with 
H. Spencer-Browne, M. B. Cantab., etc. Vol. I. 1917. 8". 
746 pages. William Wood & Co., New York. 



The Johns Hopkins HospUal Bulletins are issued monthly. They are printed by the LORD BALTIMORE PRESS, Baltimore. Subscriptions, $3.00 
a year {foreign postage, 50 cents), may be addressed to the publishers, THE JOH\S HOPKIXS PRESS, BALTIMORE ; single copies will be sent by 

mail fnr fifty cents each. Single copies may alio be procured frnm the BALTIMORE .V/'.'H'S CO., Baltimore. 



BULLETIN 



OF 



THE JOHNS HOPKINS HOSPITAL 



Entered as Second-Class Matter at the Baltimore, Marrland, Postoffice 



Vol. XXIX— No. 326] 



BALTIMORE, APRIL, 1918 



[Price, 50 Cents 



CONTENTS 



Cinq ans Apres. 

By r. C. Shattuck, M. D 

Diabetes: The Results of Past Treatment and Future Problems. 
By Elliott P. Josli.v, M. D 

A .Study of An Autoaaiglutinin Occurring in a Human Serum. 
(Illustrated.) 
By Mildred C. Clough. M.D., and I\a M. Richter, M. D. 

A Simple Method for tlic Determination of Venous Pressure. 
(Illustrated.) 
By N. Worth Buowx. M.D 

Abstracts of Papers 

The Maintenance Diet in Diabetes Mellitus as Determined Uy 
the Nitrogen Kiiuilibrium [Herman O. Mose.nthal and 
Samuel W. Clausen] ; — The Effect of Diet on Blood Sugar 
in Diabetes Mellitus. (Abstract.) [Herman O. Mose.nthal, 



Samuel W. Clausen and Alma Hiller] ;— A Rare Type 
of Bladder Ulcer: Further Notes. With a Report of Eight- 
een Cases [Guy L. Hunner]. 

Proceedings of Societies. 

The Johns Hopkins Hospital Medical Society 07 

Exhibition of a Case of P.soriasis. (Illustrated.) [Dr. Lloyd 
W. Keteo.n] ; — The Use of Relaxation Incisions in Dealing 
With Extensive Unstable Scars [John Staige Davis] ;- — 
Observations on Bird Malaria and the Pathogenesis of Re- 
lapse in Human Malaria [Lieut.-Colonel Eugene R.Whit- 
more] ; — The Preparation of the U. S. Army Triple Typhoid 
Vaccine. (Illustrated with Moving Pictures.) [ilA.TOR CO. 
Snow] ; — Recent Work on tlie Dirt'erentiation of the Para- 
typhoid Group in Relation to Disease in Man [Dr. Charlks 
Krltmwiede]. 

Books Received 99 



CINU ANS APRES 

By F. C. SiiATTi'CK. -M.D., Boston, Mass. 



Many a man lias wislied lie might return to earth and note 
the changes since his demise. I have never been of that num- 
ber, for is it not an endless chain ? One return might merely 
whet the appetite for another, stimulating desire, the extin- 
guishment of which, so the Buddliists hold, should be our one 
and constant aim. Or, what seems more likely, the return trip- 
per might find himself hopelessly out of place, thoroughly 
wretched. Probably the existing plan is best. It would seem 
wise to accept it as such, inasmuch as we have no choice. 

Absolutely without volition of my own, and without blame 
attaching to the all-highest Kaiser, if any credence can be 
given to his unwonted burst of modesty when he told us he did 
not will this war, I have been resurrected, and vouchsafed a 
glimpse of what five years can do in hospital medicine. The 
Kaiser has done his best to convince his people that nothing in 
the heavens above, in the earth beneath, or in the waters under 
the earth, takes place contrary to his will. I see it stated that 
he has been graciously pleased to ennoble God, who is hence- 
forth entitled to enjoy the prefix von — von Gott. 



' Read before a meeting of The Johns Hopkins Hospital Medical 
Society, January 21, 1918. 



In the spring of 1!J12, having reached the age limit tiien in 
force at the Massachusetts General Hospital, I was consigned 
to the tomb, and, indeed, was such a horrible example of dry 
rot — or something — that the age limit was promptly put down 
from 65 to 60. May I add that I think this a wise step, promo- 
tive of far more good than harm ? The ancient adage says " a 
young man for action, an old man for counsel." A service in 
a modern hospital is surely a sphere of action, and an old 
man's counsel can always be had if wanted. It is well for those 
who are growing or have grown old, to read, from time to time, 
mark, learn, and inwardly digest, Kipling's poem on the old 
men, as salutary as some of it may be brutal. 

The war came ; then our entrance into it, and the depletion 
of hospital staffs for the United States service. Shorthanded- 
ness became acute, and it was deemed necessary to rob some- 
thing, so the authorities at the Massachusetts General Hospital 
began by robliing the grave, holding the cradle in reserve for 
the present, and after five years of desuetude, I trust relatively 
innocuous, I found myself again in charge of a medical service 
in a hospital. Some of the changes I note after this interval, 
and some reflections thereupon form the subject of my short 
and informal talk to you this evening. 



:s 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 326 



One striking fact was the small niimber of typhoid cases. 
I think the number was diminishing while I was still active; 
but I could not help contrasting 5 per cent of medical beds 
occupied by typhoid patients with nearly 50 per cent as I have 
seen in Octobers of the past. Two of the cases in my service con- 
vey a lesson. They were a brother and an uncle of an Italian 
wlio was in the hospital in the summer with typhoid, but car- 
I'ied a bacilluria six weeks after recovery in other respects. He 
was reported to the Board of Health and by them put in another 
liospitixl where he stayed two weeks, then being discharged, as 
reported, with constant negative cultures. He went back and 
roomed with his brother and uncle, both of whom came down 
with typhoid. The original case re-entered the Massachusetts 
General Hospital and gave a positive culture. I had supposed 
hexamethylenamine to be truly specific for typhoid bacilluria, 
and, at the time of the Spanish war, I ordered the drug given 
as a routine thing to every case of typhoid. It seems, thus, 
that a few cases are resistant. The spread of typhoid tlirough 
the urine of a carrier would seem a more insidious danger than 
through the feces, a more oft'ensive excretion. The time seems 
near when it will be as hard to demonstrate a case of typhoid to 
students as it is now a case of smallpox. I was gratified to find 
that the liberal diet in typhoid, of which I was an early advo- 
cate, is still in force. What plan of diet you follow here I do 
not know, but McCrae in 1907 either had never heard of a 
liberal diet in typhoid or perhaps thouglit it too dangerous 
even to mention. 

Peptic ulcer is my next theme, i was formerly quite accus- 
tomed to the nearly constant presence in my female ward of 
several cases of gastric ulcer, almost invariably with the clinch- 
ing evidence of hemorrhage. These almost always did well 
under purely medical treatment unless there was distinct py- 
loric stenosis. I now find a decidedly larger niunber of cases in 
the male ward, often sent in for such study as the slender purse 
cannot afford outside of the hospital. The X-ray here occupies 
a more prominent position than it did, partly through improve- 
ments in methods, mainly through accumulated experience. 
Our X-ray expert, Dr. Holmes, holds the, to my thinking, 
sound view that X-ray evidence of ulceration in or about the 
upper digestive tract is corroborative rather than determinant. 
Its positive value is great when it fits in with evidence derived 
from the history, physical examination and other tests. Am 
I warranted in suspecting that some X-ray experts attach 
undue linahty to their findings ? Personally, when the X-ray 
and the other evidence diverge, I should put the X-ray in the 
second place. Let me mention two cases, among others, which 
come into my mind in which X-ray evidence would have been 
helpful. A young woman, not a bleeder either of congenital 
or any apparent acquired origin, had persistent hasmatemesis. 
I urged operation, which showed tliat the blood oozed from the 
whole gastric mucous membrane. Possibly an X-ray miglit 
have saved her from operation and from death. 

A middle-aged woman was transferred from the surgical to 
my ward as inoperable. She had coffee-ground vomit, no free 
HCl and an epigastric tumor. We all concurred in the diag- 



nosis of gastric cancer, and her friends were advised to take her 
home as speedily as possible to a neighboring state. Later I was 
told that she died of pneumonia several j'ears after discharge 
from the hospital, and that an autopsy showed her epigastric 
tumor to be a displaced kidney. 

Peptic ulcer still seems to me to belong to the physician with 
the surgeon in reserve. There can be no question as to the add i- 
tion to our power of recognition of peptic ulcer afforded by the 
ante-mortem knife of the surgeon. You all remember Dr. Wen- 
dell Holmes' comparison of an autopsy to inspection of the fire- 
works the morning after the Fourtli of July. IModern surgery 
has amplified our knowledge of the pathology of the living as 
nothing else could have done. At one time, 10 years ago, if you 
will, with the best intentions to keep an open mind, I felt that 
indiscriminate gastroduodenal surgery was in the ascendant, 
that surgery was too often regarded as a short cut to cure. I 
could not satisfy myself how gastroenterostomy could obviate 
the underlying cause of ulceration. Marked more or less tem- 
porary improvement might be accounted for by the rest wliich 
operation brought the patient and his stomach. 

I recall the case of an unfortimate young woman in my serv- 
ice who had undergone at least two operations for dyspepsia in 
another hospital. She was ungrateful enough to be no better, 
and entered to find out whether another operation might restore 
the upper digestive channels as planned by the Divine Archi- 
tect. Adhesions were separated, and the gastroenterostomy 
closed — with considerable relief up to the time of her dis- 
charge. It has been impossible to learn of the end result. 

This year I got the impression that the surgical treatment of 
peptic ulcer is more discriminating than it was. My time and 
basis for judgment were too limited for more than an impres- 
sion ; but I can see no reason to change the conservative view 
I have long held on this point. The crucial test of time and 
the gro-R'th of " end result " statistics should put us in a better 
jjosition to judge than was occupied five years ago. We are less 
patient than we used to be. We are in a hurry to " get results." 
And a clean surgeon rarely kills. 

Am I dreaming when I think 1 recall that recognized cases 
of gastric ulcer were rare in the wards of tliis hospital 25 years 
ago ? Tell me. Dr. Thayer. 

Five years ago, with us at the Massachusetts General Hos- 
pital, at least, the fresh, cold air treatment of pneumonia was in 
full swing. A head-high screen around the bed of the pneu- 
monic did something to temper the air from the open window 
to the other shorn lambs in the ward. In short, the open-air 
treatment was carried out as far as practicable in an open ward. 
This autumn the screen was still in evidence, the open window 
less so, as it seemed to me. Why then the screen ? — I asked 
myself. The ordinary pneumonias are not easily contagious, 
and a patient who is either a menace or a real disturbance to 
others should not be in an open ward. Tliough asphyxia is 
rarely a potent factor in pneumonic death, I have long held, 
and used to teach that a plentiful supply of fresh air was desir- 
able. The young and vigorous will stand, and possibly benefit 
by, a lower temperature tlian the old and feeble. The craving 



April, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



79 



of old people for warmth would seem to indicate an intolerance 
of cold, due in part, at least, to lessened activity or involution 
of the thyroid gland. Five years ago the studies of Cole and 
others on the varieties of the pneumococcus had not progressed 
far enough to help in prognosis or treatment. The routine 
effort to determine the type of pneumonia I noted as another 
innovation. Until some efficacious antidotal treatment for 
pneumonia is discovered, the mortality will remain about the 
same. Here may I express my great sympathy to you in the 
loss of Theodore Janeway? In his case surely death loved a 
shining mark. 

A paper by Dr. Charles H. Lawrence and myself will appear 
shortly, analyzing the pneumonias at the Massachusetts Gen- 
eral Hospital from 1889 to 1916, about 3500 in number. Our 
data begin where Townseud and Coolidge left off, and we find 
the mortality practically the same in the days of heroic, expec- 
tant and alcoholic, symptomatic, and fresh air treatment. I 
wonder whether the pendulum has not swung too far away from 
alcohol in cases of j)rofound general sepsis. Many of us elders 
who have lived through the unquestioned abuse of alcohol in 
disease cannot get rid of the belief that there are cases of 
sepsis in which alcohol, even in massive doses, are life-saving, 
if given with brains. I emphasize brains, for the best results 
are to be obtained only under close and skilled observation. 
All trace of alcohol in the breath should disappear before more 
is given ; so, also, any toxic effect, flushing, for instance. Fil'ty 
years from now will alcohol be considered always, everywhere, 
under all circumstances, the unmitigated poison which somi! 
present day apostles hold it to be; and which the American 
Medical Association has pronounced it to be? Fully realizing 
that what I may think cuts no ice, to use a colloquialism. 1 
doubt. Mercury and bleeding were so abused that they fell 
into disuse, but have come back. I find that in 1912 in the 
Massachusetts Hospital $551.17 was spent for alcohol as an 
internal remedy against $133.36 in 1917. The whiskey bill in 
1917 was 20 per cent larger than in 1912, but this probably 
indicates a rise in the price, not an increase in the amount. 
The following table may prove of interest : 

1908 19J2 1917 

Ale $ 94.75 $174.97 $50.95 

Beer 67.46 31.50 6.24 

Brandy 114.75 131.62 

Champagne 77.90 57.75 16.00 

Wines 20.3.08 114.83 11.13 

Whiskey 40.50 49.04 

$551.17 $133.36 

The value of the X-ray in the detection of gall-stones has 
certainly increased in the past five years. This gain I am told 
is due to a shortening of the time of exposure from 20 seconds 
to a fraction of a second, thus reducing mobility of surrounding 
parts as a source of error. 

To turn now from special diseases to the general trend of 
thought and practice in the past five years. I see real progress 
in the care and thoroughness with which the sick are studied, 
their histories and tlie course of their maladies recorded. In- 



deed, I found the records so voluminous and minute that it 
was hard to see the wood by reason of the trees. The labor 
of the chief of staff would be lightened and the mental training 
of the younger men promoted, as it seemed to me, by the addi- 
tion of a brief, clear, logical, consecutive statement of the 
essentials of each case, especially the complicated ones. The 
power of terse statement with a quick eye for perspective and 
values is worth the labor of attainment. Are dictation and the 
typewriter enemies of prolixity and slovenliness in the use of 
our wonderful language ? As an intimate knowledge of King 
James' Bible wanes, English decays. 

As I look back 50 years when I began to frequent hospitals 
seriou,sly. I note a wonderful advance in diagnostic and thera- 
peutic procedure. The major part of this, certainly in impor- 
tance, dates from the birth of bacteriology ; chemistry, and some 
knowledge of the hitherto unknown vibrations, the X-rays 
among others, are also vital factors. When I began the study 
of medicine and for years thereafter we soon came to an end of 
our means of investigating disease as exemplified in a patient, 
and could devote much of our energies to caring for the sick 
man, a human being different from any other upon earth, and 
meriting study as a sick man, not merely as a case of disease. 
With the multiplication of instruments of precision, of chemi- 
cal and other tests, psychological included, with the steady 
improvement in X-ray technique, the possibilities of study 
have grown many fold. The pace has not slackened these past 
Rve years, and some jjatients surely now have time to die or get 
well before a really scientific diagnosis is reached, and there is 
a greater chance for the patient to be forgotten in his disease. 
There is a possibility of error both in observation and in inter- 
pretation. This tendency, if it exists outside of my imagina- 
tion, is enhanced by the polyglot publicum of our wards. The 
wall of language impedes some of the currents of human medi- 
cine. Some years ago I had a census made in my ward with 
22 patients. There was only one I should call a Yankee, that 
term connoting to me a person of relatively pure New England 
blood. With many of these patients we can communicate only 
through an interpreter, not always at hand. Human fallibility 
constantly lurks behind even the instrument of precision and 
the chemical test. 

I well remember an observation dropped by the shrewd and 
kindly, old, as he seemed to me then. Dr. Tessier of the Lyons 
Hotel Dieu, 40 years ago — " Le medecin gusrit rarement, 
ameliore souvent, console toujours." To-day he cures oftener 
than he did then, for he knows far better what things are 
curable and how they are to be cured. He also relieves oftener. 
Does he as invariably and as surely console? There are still 
all too many cases in which consolation alone remains. 

While I rejoice in and try to do justice to .scientific progress, 
I should be sorry to think that any real values shrink or vanisli. 
To slightly paraphrase a saying of our Lord — " Thus ought 
we to do but not to leave the other undone." I believe in the 
perfectibility of man — in time. It is surely in place — is it 
not? — to enter a plea for liumanism on the scene where a great 
humanist scored so many of his triumphs, your and our William 
Osier. 



80 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 326 



DISCUSSION 

Db. W. S. Thayeb (Abstract).— It was my rare good fortune 
nearly 30 years ago to come into my first service in tlie Massacliu- 
setts General Hospital under Dr. Shattuck, and it has been deeply 
interesting to me to hear what he had to say. He has mentioned 
various things that have interested me particularly. 

In the first place, his observations on gastric ulcer. It is true 
that in 1890 when I first came here, for several years we had 
curiously few obvious gastric ulcers; whereas during the service of 
three months 1 had under Dr. Shattuck, we had a number of out- 
spoken cases of these ulcers. Although we had few cases then, we 
have made up for it since. I think it was simply one of those 
remarkable periods during which we had a few cases come to us. 

I was very much interested in what Dr. Shattuck had to say 
about sepsis. I confess to feeling very much as he does. I cannot 
believe that I have been absolutely deceived in the value of alcohol 
in some acute infections. When I was in the Massachusetts 
General, we were using alcohol quite freely. I remember one 
particular patient with pneumonia who was taking 36 oz. of wliis- 
key a day. I was called up one night about midnight by the nurse, 
who said she was afraid something serious had happened. I 
hastened to the ward and found an individual with a perfectly 
normal temperature, sitting on the side of his bed and singing in 
the most ribald fashion. He had had his crisis and the alcohol 
was being continued! I should not be surprised if in after years 
we do not perhaps use a little more alcohol in acute infections 
than we are employing to-day. 

It was nearly 30 years ago in the fall of 1SS8, when I came 
Into the Massachusetts General and began my service with 
Dr. Shattuck. It was a most interesting and valuable service I 
had during that year. He was a good deal the sort of doctor that 



he has described to-night, if you read through what he said. He 
was not only a very acute clinician and a remarkably good observer, 
but he taught us how to treat patients in every sense of the word. 
I never have seen one who was more able to stimulate and 
encourage his patients and who failed less in doing so. Dr. Shat- 
tuck not only taught us to observe, but he taught us what no one 
else at that time was teaching in the Massachusetts General Hos- 
pital, and that was how to record our observations. He made 
exceedingly careful bedside notes. They were sometimes long for 
us to write as house officers, but tliey were exceedingly valuable 
when written down. He taught us something more, which was 
perhaps as valuable as anything else, and that was to love him. 

Dr. Wkloh. — Just a word about Dr. Shattuck. His remarks 
bring back to me a good deal that used to be written in the Roman 
histories of my early days about succeeding consulships. Tliat is 
a very good idea, and I do not know but that it might be adopted as 
a regular thing. A man retires from his consulship, is succeeded 
by somebody else and some five years later he makes a review 
which does not necessarily represent progress, but represents 
what changes resulted from a change in consulship. That is what 
interests me particularly about Dr. Shattuck's observations. 1 
hope he will have the same opportunity to give us another five 
years' review. It would certainly be worth hearing. 

Dr. Shattuck does represent, as Dr. Thayer has said, the very 
best type of doctor, combining the scientific and the practical, the 
interest in the case and the interest in the patient. No amount 
of scientific w'ork will in itself alone make a great clinician. 
The great clinician must be a combination of that scientific inter- 
est and that practical quality, which can be acquired, although not 
always readily, which looks upon the patient not as material. 
not as a case, but as a human being. 



DIABETES: THE RESULTS OF PAST TREATMENT AND 
FUTURE PROBLEMS' 

By Elliott P. Joslin, M. D., Boston, Ma-ss. 



At tlie beginning of 191-1, the outlook for diabetic patients 
was depressing. The statistics of tlie Massachusetts General 
Hospital showed that in the preceding 16 years for each 100 
diabetics admitted 28 were discharged dead, a record which 
duplicated the experience of the hospital between 1824 and 
1898. Physicians dreaded to place their patients in an insti- 
tution lest the treatment there jirescribed prove more disas- 
trous than that adopted by the patient's fancy. Surgeons 
dodged the diabetic, while the obstetrician was out and out 
afraid of diabetes and urged pregnant women to have abortions. 
The neurologist, dermatologist and ophthalmologist would 
throw up their hands at complications within their ri'spcctixc 
spheres and exclaim. " Cure the diabetes and then wo will help 
the patient." It is hard to realize that these conditions pre- 
vailed only four brief years ago. 

As so often happens when the clouds are darkest, light un- 
expectedly appears, and 1 recognized its approach one after- 
noon while talking with Dr. Allen. Tt happened in this way: 
We were discussing one of my severest cases (Ca.se No. 341) 
and I pointed out how (lie type of diabetes in this instance 
changed from severe to mild :i- tuberculosis came on and the 



' Presented before Tlie .Johns Hopkins Medical Society, Feb- 
ruary 4, 1918. 



patient progressively became weaker and lost weight. 1 remem- 
ber telling Dr. Allen that if he could explain why this change 
took place the problem of diabetic treatment would be greatly 
advanced. The next day 1 heard from him that he felt be could 
explain the reason for the improvement, and furthermore lic- 
lieved that he would be able to demonstrate the cause for it liy 
animals, and soon after 1 was gratified to learn bow doctors 
could give their diabetic patients renewed hope. You are fa- 
miliar with his experiments by which he showed that dogs made 
artificially diabetic and then forced ])rogressively to lose 
weight gained in tolerance for carbohydrate. 

The far-reaching results of these experiments imnu'diatcly 
began to show, and nvv illustrated by the following (able: 

TABLE 1 

TiiK Recent Iiupuovemknt in Diauetks as Shown bv the 

Statistics op tub Ma.ssaciiusetts General Hospital 



Mortality during hospital sta 



I'crioH 

1824-1898 

1898-1914 284 

1914 

1915 

1916 

1917 



cases '' 


No. of deaths 


PC 


r cent 


172 


47 




27 


284 


80 




28 


.'il 


,s 




16 


89 


11 




12 


103 


s 




8 


105 


6 




6 



April, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



81 



Your attention is directed to tlie stationary character of 
liospital diabetic mortality for 90 years and its abrupt and 
steady diminution following Dr. Allen's announcement. A re- 
duction of mortality from 27 per cent to 6 per cent would 
appear to be sufficient proof of improvement, but other evidence 
is available. At the New England Deaconess and Corey Hill 
Hospitals there were under my care during 1917, 181 diabetic 
patients. Of these four died, a mortality of 2 per cent, and I 
believe that this year three of these patients could be saved. I 
have summarized my personal statistics in Table 2. 

TABLE 2 

Author's Statistics of Diahetic Patients Treated at the New 

E.NGLAXD Deaconess and Corey Hill Hospitals 

Mortality during hospital stav 

No. of , -• , 

Year cast's No. of deaths Per cent 

, 1913 43 4 9 

1914 60 3 5 

1915 109 6 6 

1916 164 S 5 

1917 181 4 2 

Wl)at other disea.sc, chronic or acute, can show a simihir 
reduction in mortality during these last four years ? After all, 
diabetes has points in its favor. Never forget that unlike can- 
cer and rhemnati.sm, it is painless ; unlike tuberculosis, it is 
clean and not contagious, and in qontrast to many diseases of 
the skin, it is not unsightly. Moreover, it is susceptible to treat- 
ment and the downward course of a patient can usually be 
promptly checked. It is true that treatment is by diet and not 
by drugs, but the patients who know the most, conditions being- 
equal, can live the longest. There is no disease iu which an 
understanding by the patient of the methods of treatment avails 
as' much. Brains count, though knowledge alone will not save 
the diabetic. This is a disease which tests the character of the 
patient, and for successfully withstanding it, in addition to 
wisdom, it demands of the individual honesty, self-control and 
courage. 

This striking improvement in diabetic treatment belongs 
to the first year of the disease, the year which I call the dia- 
betic's danger zone. This is important, for it is the most use- 
ful year to the diabetic and to the community. The first year 
of the disease is pre-eminently the year of coma. Eighty-seven 
per cent of all diabetics who have come under my care and have 
later died during the first year of the disease have succimibed to 
it. And yet to-day everyone will agree that diabetic coma dur- 
ing the first year of the disease should be considered an acci- 
dent which can and shovdd be avoided not only in adults but in 
the youngest child. ' 

How much the average lengtli of life of the individual patient 
has been increased by our recent methods no one knows, Init 
the following table gives my own personal experience, ending- 
December 1, 1916. Eventually I hope to bring this table up to 
January 1, 1918, and to continue it still further. As it stands 
now the average length of life of my fatal cases for the different 
decades is considerably under the average length of life of the 
living cases. This is a hopeful sign. 



TABLE 3= 

Duration of Life of Fatal and Living Cases of Diabetes, 

December 1, 1916 

Fatal Living 
^ ^ A ^ 

Age at onset Average Average 

years No. cases duration No. cases duration 

0-10 37 1.3 22 2.6 

11-20 .55 2.8 40 2.9 

21-30 51 3.1 61 5.3 

31-40 64 4.4 94 7.2 

41-50 95 6.4 184 7.3 

51-60 115 6.9 163 6.3 

61-70 67 5.7 63 6.1 

71-80 16 3.6 12 5.3 

81-90 ... 1 1.3 

The prolongation of life holds quite as strongly with the 
young as with the old. It was rare formerly for a patient 
in the first decade of life to live more than a few months. Now 
the children are expected to live at least twice as long. This 
may not mean much in itself, but it does in the treatment of 
diabetes as a whole, and it demonstrates that if the duration of 
the disease in the severest cases has been doubled by the im- 
Ijroved methods of treatment, marked gains iu treatment ought 
to follow in the mild types. With the middle-aged I have been 
able to collect from my records 33 cases who have not only lived 
long, but have exceeded their theoretical expectation of life at 
the onset of their diabetes. Jloreover, nearly a year ago Hor- 
nor and I ° found that 5 per cent of the cases had lived over lo 
years. 

Mention was made of the surgeon's and obstetrician's avoid- 
ance of the diabetic patient in 1914. To-day I can testify from 
my own experience that without fear and with success surgeons 
remove the appendix, uterus, ovaries, prostate, gall-stone.s ; 
resect cancers of the bladder or large areas of int€stine on 
account of strangulation, and even operate on the lung. The 
obstetrician now carries his patients through labor without 
danger and there are a good many healthy children living to- 
day whose lives are a witness of improved diabetic methods. 
Neuritis and affections of the skin are rare exceptions. On 
January 26, 1918, Case No. 817, whose carbimcles were so 
extensive three years ago that the attending physician felt it 
was kindness to allow him to die, came into my office at the age 
of 76 years, having gained 59 pounds since I first saw him ! I 
confess that it is not often that the diabetic of so many years' 
duration complains as did he of growing fat. 

Improvement is also registered by successively severer and 
severer cases being rescued from coma. Six months ago I was 
able to publish a list of 15 severe cases of diabetes recovering 
from acidosis, with subsequent discharge from the hospital, 
without the use of alkalis.* Estimating the severity of these 
cases in terms of carbon dioxide tension of the alveolar air or of 
the blood, their acidosis was included between the boundaries of 



= Joslln: Treatment of Diabetes Mellitus, 2d Edition, Lea & 
Febiger, Philadelphia, 1917. 

' Am. Journ. Med. Sciences, 1918. Vol. CLV, p. 47. 
* Joslin: Lo-: lit.. Table 172, p. 389. 



82 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 326 



15 and 25 mm. mercury. Compiling a second series one montli 
ago I was able to substitute seven cases in the original list by 
seven others still more severe, thus changing the limitations of 
the carbon dioxide to between 14 and 22. In anticipation of 
this meeting, I wrote Dr. Geyelin of' New York and he has 
furnished me with cases of his own and at least three of these 
will replace three of mine, thus enabling a new series of 15 
cases to be compiled of threatening coma treated successfully 
without alkalis, of which, thanks to Dr. Geyelin, the lowest 
limit, measured in terms of carbon dioxide tension, is reduced 
to 13.65 mm. mercury in the blood, and the highest limit to 20, 
measured in terms of carbon dioxide in the alveolar air. These 
results arc shown in Tables -i and 5. 

TABLE 4 

Threatened Diabetic Coma Successfully Treated WrniorT 
Alkalls. Three Groups of Cases, 15 Each, Co.mpiled at 
SuccEssrvE Dates, Each Group Severer tii.\x the Pre- 
ceding. 

Limits of degrees of acidosis 
Date of C0» in terms of mm. Hg. in 

conipiiutioii No. cases blood or alveolar ail 

September, 1917 15 15-25 

January. 191S 15 14-22 

February, 191S 15 13.7-21 

TABLE 5 

Successful Tre.\T-Ment without Alkalis of 15 Cases of 
Diabetes Thre.\tenki) with Cojia 

Hlood Alveolar 

NH., C0„rnm. air CO, 

Case No. Date KcCl. grams fig. mm. Hg". 

691 Nov. 15, 1917... + 20 

1200 May 29, 1917 ... + + + 2.3 .. IS 

786 June 11, 1916. .. -f+ 3.9 .. 18/20 

12 + 3.2 24 21 
Dr. Geyelin May 31. 1917. .. + + + + + ... 13.7 .. 

J. G. 

942 July 12, 1916... + + + 4.4 20 20 

13 ++ 3.7 .. 17 
938 Nov. 2, 1917 + + + + 1.3 .,. IS 

Dr. Geyelin Apr. 5, 1917 + ++++ ... 21 

M. S. 

Dr. Geyelin Oct. IS, 1917... + + + + + ... 16 

H. J. 

755 Apr. 15, 1917... + 1.6 .. IS 

1011 Mar. 29, 1916... ++ l.S .. 23 

Apr. 13, 1916. . . ++ 22 

Sept. 25, 1917... + + + + 15 

1085 Oct. .30. 1916 ? 1.7 28 20 

1196 Dec. S. 1916 + + + + 4.6 .. 21 

9 ++ 6.0 26 22/14 

10 + + + 3.3 .. 18/20 

11 +3.1 26 20 

12 ++ 3.3 .. 21 

13 ++ 2.9 .. 24 
1070 June 23, 1916. . . ++ 1.9 21 20 

1012 Sept. 13, 1917 .. + + + 14 

14 + + + 2.5 21.3 14 

15 ? 2.3 .. 16 
1120 Sept. 6, 1916 ... + + + 21 

7 + IS 

Oct. 11. 1916 ... ++ 1.9 .. 22 

14 20 

27 + 15 



Individual cases are more striking than convincing. Each 
month I derive encouragement from the return of an old case. 
A recent one is Case No. 866, first seen in 1915 at the age of 
32 with onset one year before, whose consumption of food prior 
to admission to the hospital in 1915 was extraordinary even for 
a diabetic. His regular ration was two dozen eggs, tliree 
pounds of meat and 30 apples, with other food unrecorded. 
The sugar in the urine at this time amounted to 4 per cent. 
On January 28, 1918, he again returned to the hospital, after 
an absence of three years, but this time sugar and acid free 
and with the report of having remained so almost constantly I 
During the interval he had at no time gone to a physician's 
office and at no time missed work on account of ilLuess. His 
present diet and method of living interested me extremely, for 
it shows what a courageous man can do. It consists of a pound 
of cahbage at each meal, and for the day two eggs, 60 grams of 
bacon (weight uncooked), sLx ounces of meat at dinner and the 
same for supper, 120 e. c. of 20 per cent cream, and about 60 
grams of butter. I do not report this as an ideal diet, but upon 
it this man has supported his family and lost but six and onc- 
lialf pounds in weight in three years. Mark this ! He retires 
at 8 p. m. and rises at 6 a. m., 10 hours in bed ! The course 
of this case should be compared with the course of patients 
who suffer from other chronic diseases. How many nephritic, 
cardiac, arteriosclerotic or chronic rheumatic patients could 
touch as low a limit of life as this patient three years ago and 
regain to such an extent their efficiency ? 

I do not share the opinion of some hospital clinicians who in 
the face of cases like this, and in these da}'s when the hospital 
diabetic mortality has been lowered from 28 to 2 per cent, pre- 
tend to be discouraged about the treatment of diabetes and are 
prone to fill their wards with i^atients showing interesting clec- 
troeardiagrams whose efficiency can seldom be regained. 

Will the recent improvement in treatment continue ? I be- 
lieve it will, and for three reasons. First of all, the trend of sta- 
tistics points to it, as is proven by a study of the statistics of the 
^Massachusetts General Hospital. You have undoubtedly 
observed that the reduction in hospital mortality has taken 
place gradually. Each year has shown progress, and my own 
figures illustrate that this improvement can proceed still 
fui'ther. In the second place, the enemies of the diabetic are 
now more clearly recognized. We know exactly witli what wc 
must contend. This is evident from Table (i. 

TABLE 6 

Causes of Death of 516 Diabetic Patients Seen in Private 
Pr.\ctice On^-. or More Times from 1894 to Dec 11, 1916 

Coma 60 per cent 

Cardiorenal 13 " " 

Infections 10 " 

Cancer 5 " " 

Tuberculosis 4 " " 

Inanition 1 " " 

Miscellaneous 6 " " 

I would particularly dircci your attention to the 60 jier cent 
of deaths due to coma and the 1 per cent of deaths due to inani- 



ApraL, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



83 



tiou. Since fasting treatment, introduced by Dr. Allen, has 
been adopted, the fear has arisen that inanition would figure 
prominently as a cause of death of diabetic patients. As yet 
this has not proven to be the case. Inanition will undoubtedly 
iucivase in frequency, but I shall not allow it to divert my 
attention from tlie 60 per cent of the cases who die of coma. 
All Init two of my fatal cases in children have died of coma. 
Of all the diabetics coming under my supervision, 87 per cent 
of those who have died during the first year of the disease have 
succumbed to coma, and even 44 per cent as well of those cases 
who have lived more than 15 years. The one enemy which the 
diabetic must fight is coma. Thirteen per cent of the patients 
died of cardiorenal disease, but with modern treatment 
adapted to impaired kidneys the lives of such imtients might 
be easily prolonged. Infections continue to be a great menace, 
but are not nearly so serious as formerly, when they were so 
often complicated by coma. AVe must expect that the mortality 
from cancer will rise, and can look for a continued lowering 
in tlie mortality from tuberculosis due to the lessened oppor- 
tunities for contagion. It is better avoided than treated, but 
even if present does not preclude many years of life. 

The third reason for the continued improvement in the treat- 
ment lies along several lines. (A) Earlier diagnoses of the 
disease are being made. By this means, mild cases are dis- 
covered and their change into a severer type is delayed or pre- 
vented. (B) Coma can be avoided to-day in the overwhelm- 
ing majority of cases. Whereas formerly mmiberless diabetics 
died at the beginning of treatment, to-day such a death excites 
comment in any well-regulated liospital. Attention has been 
called to the decrease in coma after surgical operations due to 
the measures adopted to prevent acid-poisoning and the de- 
creased use of ether as an anesthetic. (C) A new type of 
ammunition in the battle against diabetes is now being gen- 
erally adopted. I refer to the education of the doctor, nurse 
and, most of all, the patient. AYhether teacher and student 
desire to devote increasing time to the study of diabetes, the 
fact remains that there are four times the nimiber of cases in 
the United States recognized to-day as in 1890, and thus four 
times as many to be treated. Instruction in diabetes, therefore, 
should receive four times the time allotted to it in the cur- 
riculum. Diabetes is pre-eminently a disease in which educa- 
tion avails. Fortunately, with the treatment introduced by Dr. 
Allen, the education both for doctor and patient has been so 
sini|ilili('d that tlic essential facts can Ije summarized on a small 
card. 

The training of the patient in hygiene, diet and clinical tests 
constitutes a new era in medicine. Previously tuberculosis was 
the disease where the education of the patient was most in- 
sisted upon, and in that hygiene alone was the only suljject 
taught. Many advantages will accrue from the war and not the 
least of these is the compulsory education of patients and of 
nurses in matters hitherto supposed to be beyond their ken. 
To-day I know a group of nurses who specialize in diabetes, and 
I can trust any one of these nurses to go into a patient's home 



and carrj' out treatment from beginning to end, simply depend- 
ing upon the family physician for general supervision. 

The Treatment of Diabetes as Practiced To-day. — The treat- 
ment of diabetes as it is actually practiced to-day is very dif- 
ferent from wdiat it should be. By no means does it follow the 
lines advocated at the Kockefeller Institute, The Johns Hopkins 
Hospital or other large hospitals in the country. I honestly 
believe that more cases of diabetes are now treated with the diet 
which appears on the back of a drug firm's advertisement than 
by any other method. It is still a rarity for a patient to come 
to me free from sugar and free from acidosis, and the cases are 
few and far between who have any conception of dietetic values. 
Diagnoses of diabetes are still made too late. Unfortunate as 
this is, I am glad to say that I have noted definite signs of 
improvement, chiefly manifested in the l^sened use of drugs. 
The general practitioner is not to be too sharply criticized, 
because the methods which are employed in the leading institu- 
tions are only of recent origin, and furthermore, the general 
practitioner has never had a consistent plan for the treatment of 
diabetes laid out for him. It would be a great mistake if our 
present simple methods were to be rapidly changed purely for 
the sake of some slight improvement. When we realize the 
great advance in the treatment of diabetes which has taken 
place during the last four years, and at the same time bear in 
mind the intricate but definite problems which lie ahead, and 
appreciate the difficulty of interpreting the mass of scientitie 
data just accumulated, we should hesitate long before altering 
the methods which have brought these gains. In the past, 
waves of diabetic treatment have followed in rapid succession. 
From nearly each one of these something has been gained. Let 
us be sure that we gather the benefit of all the good which is 
coming in on the present crest before we dive into a new 
breaker. 

What Should be the Treatment of To-Daij? — In general, 
authorities agree. The patient should be made sugar-free and 
this should be done in such a manner as not to produce acid in- 
toxication. The basic principle is fasting, and it makes little 
difference whether the fasting is absolute or partial. Some of 
us prefer to omit the fat in the diet before the fast in the hope 
of warding off acid poisoning, which occurs in a small number 
of cases following the fast. This method has been most satis- 
factory in my hands. By this means, along with the preven- 
tion of acid poisoning, the patient gets the benefit, without the 
hardships, of reduced calories. The rules which I follow in the 
treatment of my cases are very simple, and although I seldom 
follow these to the letter, for each case is unto itself, I have 
found the method of treatment so satisfactory that I shall 
lierhaps be more loath to change it than those of you who arc 
just starting in medicine and have not lived through the barren 
years of diabetic treatment. These schematic rales and the 
dietetic values necessary for the patient are recorded on this 
small card, the reading of which may be omitted. 

Preparation for Fasting. In severe. long-stanaing. compUcated. obese. 
and elderlv cases, as well .is in all cases wUh acidosis, or in any case it 
desired, without otherwise changing habits or diet, omit fat. after two days 
omit protein, and then halve the carliohydrates daily until the patient is 
taking onlv 10 grams ; then fast. In other cases begin tasting at once. 



84 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 32G 



Fasting. Fast four days, unless earlier sugar-froe. Allow water freely, 
tea. coffee, and tbin. clear meat broths as desired. 

Intermittent Fasting. If glycosuria persists at the end of four days, 
give 1 gram protein or 0.5 gram carbohydrate per kilogram body weight 
for two davs. :ind tlicn fast again for three days unless earlier sugar-free. 
If glycosuria remains, repeat and then fast for one or two days as 
necessary. It there is still sugar, give protein as before for four days, then 
fast one, and then gradually increase the periods of feeding, one day each 
time, until fasting one day each week. 1 have seen no uncomplicated 
case fail to get sugar-free by this method. 

Carbohydrate Tolerance. When the twenty-four-hour urine is tree from 
sugar give 5 or 10 grams carbohydrate (l.iO to 300 grams of 5 per cent 
vi'gctables) and continue to add .5 or 10 grams carbohydrate daily up to 
50 grams or more until sugar appears. 

Protein Tolerance. When the urine has been sugar-free for three days, 
add aliciiil I'll yranis protein and thereafter 15 grams protein daily in the 
form of iK^' wliiii'. lisb or lean meat (chicken) until the patient is receiving 
1 giiim ]. rut. ill piT kilogram body weight or less if the carbohydrate 

tollMMlI.e is Z.T.I. 

Fat Tolerance. Add no fat until the protein reaches 1 gram per kilo- 
gram li.iilv \v.i;;ht (unless the protein tolerance is below this figure) and 
tlie carli.ihy.lrat.- tolerance has been determined, but then add 5 to 25 grams 
daily ;n-i-.ir(ling t.i pr.'\'ious acidosis until the patient ceases to lose weight 
.jr I'p.i'ivis in 111.' i.itaj diet about 30 calories per kilogram body weight. 

Reappearance of Sugar. The return of sugar demands fasting for twenty- 
f.iiir b.iiirs. ..r until siiyar-f ree. Resume the former diet gradually adding 
fat last in ord.-r t.i in;iiiitain as high a carbohydrate tolerance as possible, 
sacrificing body weiu^lil for this purpose. 

Weekly Fast Days. Wli.n.ver the tolerance is less than '20 grams 
carbohydrate, fasting should be practiced one day in seven; when the 
tolerance Is over 20 grams carbohydrate cut tile diet in half on one day 
each week. The foods commonly employed in determining the tolerance for 
carbohydrate and protein are .5 per cent vegetables, oranges, oatmeal, 
potato, fish, chicken, lean meat. 



1 gram protein. 4 c 

1 " carbohydrate, t 
1 •■ fat. '.1 

1 " alcohol, 7 

protein contain Ig. 



G.2 



Ikilogram = 2.2 pounds. 

30 grams (g) or cubic centimeters 
(c. c. ) — 1 ounce. 

A patient at rest requires 25 cal- 
ories per kilogram body weight ; 
approximately 1 calorie per kilo, 
per hour. 



Consult Chemical Composition .\merican Food Materials. Bull. 28. f. S. 
Dept. Agriculture, by sending 10 cents in coin to Supt. of Documents, 
Washington, D. C.. also Annual Keport Conn. Agricultural Experiment 
Station. New Haven, Conn., Food Products and Drugs, 1913, Part 1, 
Section 1. — Free. 



Water, clear broths, coffee, tea, cocoa shells and cracked . 

without allowance for food content. 



can he taken 



Foods AttRAXGEu Ai'Itioximatelv Accokdi.n 
Carbohydrates 



TO CO.N'TEXT OF 



„ 


5% • 


10% • 


15% 


20% 


■S Lettuce 


Tomatoes 


Pumpkin 


Green Peas 


Potatoes 


£ Cucumbers 


Urussels 


Turnip 


Artichokes 


Shell Beans 


3 Spiiia.'b 


Sprouts 


Kohl-Rabi 


Parsnips 


Baked Beans 


S Asparagus 


Water Cress 


Squash 


Canned 


(Jreen Corn 


.n Itliiiliarb 


Sea Kale 


Beets 


Lima Beans 


Boiled Itice ' 


J Knilivi- 


(ikra 


Carrots 




Boiled 


t; Miirniw 


Cniilill.iwer 


Onions 






v> .s..rrel 


Iv.-^ IMant 


Mushrooms 






'^ Saii.TUnnit 


k-i.lislTes 










Suing I>.,.ans 








S Swiss Chard 

> Celery 


liroccoli 








f!i|ie illlves 


20% fnt) 


Oranges 


Apples • 


Plums 




Cranberries 


Pears 


Bananas 


f^ T.'iiioiis 




Strawberries 


Apricots 









Rlackberries 


Blueberries 






(tooseberries 


Cherries 




N 




Peaches 

Pin..iip|il,. 

Wnt.rni.-I.in 


Currants 

liasjiberrles 

lliu'kleberries 




■S Hutternuts 
2 Pignoiias 




l;iiK:il .Nuts 
I'.U, WiilniKs 
Hi.ki.rv 
r.'.'.'iiis 


.Miii.inds 
Walts (Eng.) 
l!...,linuts 
I'islai-hios 


Peanuts 


• rnswe..t,ii,'. 
.= Pickl.-. 1 


Jll.l 1 lis|.i,-,..l 


40% 


= Scall..|is. 


.i^.■|■. I'ish Itnv 


Filli.'rls 


I'iiiH Nuts 


Chestnuts 



' Reckon carb. 



of 



group as 37r — of 10% group as 



(30 grams 1 oz.) carbohydrates 

contained ai>pho.xi.matei,y fl 

Oatmeal, dry wgt 20 

Cream. 40% 1 

20% 1 

Milk 1 r, 

Brazil Nuts 2. . , . . . 

Oysters, six 4 

Jleat (uncooked, lean ) 

' " (cooked, lean) 

Bacon o 

Cheese d 

Egg (one) (I 

Vegetables ,5% group 1 

Vegetables 10% group 2 

Potato I) 

Bread 1,S 

ButtiM- 



.120 
120 
. 60 



haddock (cooked) . 



Oil 
Fish, 
Broth 
Small orange or Vi 
Form ,1 H. Tluu 



grape fruit li 
IS Croom & Co 



Inc.. 105 State St., Boston 



Throughout the course of treatment the education of the 
patient in the hygiene of his life, in his diet and in the examina- 
tion of his urine should be promoted. Like others, I have 
devised various forms of printed matter, and in fact have just 
completed for jiatients a sort of diabetic primer ' which I hope 
they will actually study. This is designed not only to educate 
the patient, but to save the physician's time. 

Acidosis should be prevented by the rules of diet prescribed 
by the doctor and adopted by the patient. In general, given a 
patient without acidosis, one can avoid its onset. The elimina- 
tion of fat at the beginning of treatment and its elimination 
later wlienever signs of acid poisoning appear is a safe rule. I 
have not used alkalis for some years. Until a group of cases, 
more severe than the 15 already cited, is reported to have re- 
covered by some other method, I recommend to your considera- 
tion tlic plan of treatment which has yielded these results. 

The Treatment of Threatening Diabetic Coma 
The following rules are in force at the Xew England Dea- 
coness and Corey Hill Hospitals: 

1. Nursing. — Provide a special nurse for the patient both 
day and night, and, preferal)ly, one trained in diabetic work. 

2. Bed. — Keep the patient in bed and warm. Avoid loss of 
calories through exertion or exposure ; if restless, protect from 
becoming chilled by flannel night-clothes. Every effort should 
be made to allay nen'ousness and discomfort, 

3. Bowels. — !Move the bowels by one or more enemata. 
Cathartics sliould usually lie avoided for fear of causing diar- 
rhea. 

4. Stomach. — The stomach should lie fri-c I'miii indiocstible 
food. With adults, when in doubt, but with tiiildren in all 
cases, begin treatment with gastric lavage. 

3. Heart. — Sustain the circulation with the help of digitalis. 
Caffein may hv ijivcii subcutaneously, or as black coffee by rec- 
tum. 

(i. Aitiiiiiiistnition of Liquids. — (Jive 1000 c. c. of liiiuids 
within each six hours. The liquids are to be given slowly, liot. 
as coffee, tea, tiiin broths, water: if the prospect is dubious of 
giving so much liquid by mouth, salt solution or tap-water is tn 
be given by rectum ;, if this resource fails, the nurse should call 
the doctor to give intravenously the balance of tiie liter wbii li 
remains not given for the period. (It will seldom be found 
necessary to give more than iOOO c. c. liquids, thanks to tlic 
avoidance of alkalis,) In nnlcr to secure the introduction >'( 
sufficient liquid in the first six hours the cleansing enema at the 
beginning of treatment should be followed after half an hour 
by an enema nf ."iOO c, c, salt sdlutinn in all cases as a matter of 
precaution. 

7, Diet. — If the patient has been accustomed to the fasting 
method of treatment, begin or continue the fast, but if he has 
been upon a full diet, give 1 gram of carbohydrate per kilo- 
gram body weight during the 24 hours in the form of orange 



'A Manual of Diabetic Treatment for i:)octor and Patient, Lea & 
Febiger. Philadelpliia, 1918. 



Apkil, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



85 



juice or gruel (oatmeal) made with water; or as many gram? 
of carljohydrate as the patient has voided in the urine in each 
successive preceding six hours. Whichever course is adopted, it 
is to be followed until danger is over. 

8. Alkalis. — Avoid alkalis. If such have been previoush^ 
given, omit at the rate of 30 grams a day. 

Many diabetic problems demand solution to-day, and it is 
encouraging that they stand out in relief far more distinctly 
than ever before. Many of these jDroblems do not require great 
discoveries for their elucidation, but simply plain hard work. 
Thanks to Dr. Allen, it is fortunate that so many of these can 
be worked out iipon animals. By this means results can be 
more quickly secured. 

1. The one question which I hope most to see solved witliin 
the next two years, is whether the tolerance of a mild diabetic 
for carbohydrate is lowered by our present methods of treat- 
ment in making him sugar-free. Perhaps Dr. Allen has already 
settled this jwint. Clinically, every once in a while one sees a 
l^atient with a liigli tolerance wlio loses the tolerance in a com- 
paratively short course of time, although the best modern meth- 
ods are followed. Thus Case No. 914, with a tolerance for 140 
grams carbohydrate a year and a half ago, has now a tolerance 
for but 10 grams. This is so different from what I expected to 
•occur in this case that I can hardly believe it necessary, and 
wonder whether some error in treatment has not been made. 
Of course it is possible that a year and a half ago by our former 
methods the tolerance would not have aj)peared nearly as high, 
and that at the start the case was really far more severe than 
was considered. I am sure that many of you have had similar 
experiences. We should not allow these apparently mild eases 
to change to severe without tlie sharpest possible fight. This 
question is of the utmost importance. Take, for example, two 
children in one family living not far from this city, who have 
apparently very, very mild diabetes. Should they be kept 
absolutely sugar-free or upon a restricted diet, but not a diet 
of undernutrition ? This is the sort of a problem for the solu- 
tion of which your wealthy diabetic should give your hospital 
$o0,000. It demands both clinical and experimental work, and 
it is justifiable to hold out the hope of securing useful results. 

2. The next problem to interest me is wliether the tolerance 
of the diabetic can be raised. Already considerable data have 
been accumulated at the Nutrition Laboratory of the Carnegie 
Institution by Benedict and myself, and eventually this will be 
published. In it are hints of such a possibility. The spec- 
tacular absence of sugar in the urine following the administra- 
tion to the severe fasting diabetic of large quantities of levulose 
and of some other carbohydrates is encouraging. How these 
patients can bear so much carbohydrate at one time when at 
another a few leaves of lettuce cause glycosuria is hard to 
understand. Tlie fact tliat repeatedly the respiratory quotient 
rises in such individuals is of significance, just as is the higli 
respiratory quotient of severe diabetics during fasting. 

3. The increased lipoid content of the blood and the measures 
necessary to reduce it is a third problem. The 400 analyses of 
blood lipoids made by Gray upon my patients have interested 



me greatly, and have shown the need for more. From 
them I am beginning to learn a few suggestions as to how the 
fat can be reduced. But when I heard the other day that in 
addition to the numerous analyses made under Dr. Allen's 
direction upon the blood lipoids of his patients there stiU re- 
mained 5000 more specimens to analyze, I could not help 
feeling that perhaps we were nearer to the discovery of the 
method by which tlie higli blood fat could ha reduced than we 
supposed. 

4. The high blood sugar and its reduction in diabetes is a 
tempting target. Is this really worth while ? I think it is, but 
I would be glad to have more evidence. When I see a patient 
who has outlived the average period of life of my living cases 
for the corresponding decade of age, who appears in good con- 
dition, as does Case No. 600, and yet shows a lilood sugar of 
0.21 per cent, but is sugar-free, I hesitate to change the method 
of treatment which has worked so well so many years. Time 
perhaps will settle this question for us, for who knows how long 
this patient has had so high a blood sugar ? During the first 
five or six years of her treatment, no blood sugar test was made. 
To me it appears that she will live for many years to come, and 
although she may not reach her expectancy of life, which would 
mean a duration of the diabetes of 21 years in her special case, 
yet there appears to be a fair chance of her doing so. AVould 
this patient really be benefited, now that she is sugar and acid 
free, by having her blood sugar brought to normal ? I never 
see her without thinking, " Fools step in where angels fear to 
tread," and at present I want to be numbered with the angels. 

5. Edema and even anasarca in the severe diabetic are symp- 
toms often accompanied by well being on the patient's part. 
Why do some diabetics feel so much better ,when they have 
dropsy than when the water content in their tissues is normal 
or even below normal ? At present I can remember but one of 
my diabetic patients who lias shown marked dropsy who has 
not been freed of it by simple restriction of salt. Just recently 
1 have reported '' one case. Case No. 1012, where a gain of 25 
per cent weight in the form of edema was present, and another 
patient now under my care has lost an equal amount. If 
jiatients do not go into coma when they have drojjsy, why not 
make them have dropsy when coma is threatening? Dr. Hornor 
and I have partially attempted this in one case, but I would like 
to have it literally carried out and see the patient's weight 
increase not one or two pounds in the course of a day, but by 10 
to 20 per cent. It would not do to inject so much fluid directly 
into the circulation because of the failing heart, but tlie fluid 
could be introduced under the skin or into the abdominal cavity. 

These are only a few of the diabetic problems which you have 
to solve. Most of them appear capable of solution. They will 
not be settled except by aid from many workers, and in their 
solution not alone should the help of doctors and medical stu- 
dents be utilized, but that of technicians to the widest possible 
degree. While absorbed in our endeavors let us not forget that 
when a diabetic life is prolonged for even a day, fresh hopes 
for millions of diabetics throughout the world are created. 



' Med. Clin, of North America, January, 1918. 



86 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 32G 



A STUDY OF AN AUTOAGGLUTININ OCCURRING IN A 

HUMAN SERUM 

By Mildred C. Clough, M. D., and Ina M. Eichter, M. D. 
(From the Medical Clinic of The Johns Hopkins Hospital) 



Autoaggiutiiiatiou, tliat is, agglutination of red blood cdr- 
puscles in the presence of serum from the same individual, 
is an extremely uncommon occurrence in human beings. In- 
deed, some authors (1, 2, 3) state that this never occurs. The 
following instance is reported on account of certain interest- 
ing observations brought out in a study of the autoagglutiuin, 
as well as on account of the rarity of the condition. This 
phenomenon was first noticed in our case on making a routine 
red blood cell count. It was found upon drawing the blood 
into the diluting pipette that the red blood cells became aggluti- 
nated so markedly that clumps were visible macroscopicaUy as 
well as microscopically. The agglutinated cells could not be 
broken up upon shaking, and an accurate count of them was 
impossible. 

The literature on the subject of autoagglutinatiou is ver}- 
meager. The first reference to this phenomenon is by Reit- 
mann (4) in 1890. He noted, on making a red blood cell count 
in a case of cirrhosis of the liver, that " the red blood corpuscles 
were strikingly sticky, three or four sticking together." No 
further observations on the blood are recorded, but it seems 
likely that this occurrence was due to autoagglutinatiou. 
Ascoli (5) in 1901, stated that, in a study of the blood of 17 
normal individuals, he found in a number of instances that 
the serum was able to agglutinate the red blood corpuscles of 
the same individual, as well as those of other individuals. This 
report, however, is open to question. It seems very improbable 
that this rare phenomenon should occur a number of times 
among only 17 specimens of blood examined. This surprising 
statement is probably to be explained by the fact that he appar- 
ently regarded rouleaux formation as a form of agglutination. 
Klein (6) in 1902, noticed autoagglutination in the blood of a 
horse and stated in this report that in 1890, in a case of hyper- 
trophic liver cirrhosis, he was unable to make a red blood cell 
count, because the cells, when drawn into the diluting fluid, 
stuck together in masses in which the cell boundaries could 
scarcely be made out. He considered it a phenomenon pecu- 
liar to liver cirrhosis, and said that Obermayer in Nothnagel's 
clinic stated in a personal communication that he had confinned 
Klein's observation in a series of cases of hypertrophic liver 
cirrhosis, Landsteiner (7) in 1903, again noted autoagglu- 
tination in the blood of horses and other animals. He 
found that the agglutinin was fixed to the cells at low temper- 
atures, and if the washed, agglutinated red blood corpuscles 
were suspended in warm salt solution the clumps broke up, and 
agglutinin could be demonstrated in the salt solution. He 
considered that cold exerts a favoring influence on isoagglu- 
tination also, and that isoagglutinins can be partially lib- 
erated by warming (8), He isolated the auto- as well as the 
hcteroagglutinins in the globulin fraction of the scrum (7), 



Hektocn (!)) in l!i06, stated tliat he observed autoagglutina- 
tion and autophagocytosis in the blood of two individuals, but 
in a later article (10) said that " autoagglutinins are very 
seldom, if ever, demonstrable in vitro." Rous (11) has pro- 
duced autoagglutination in the blood of rabbits, and Ottenberg 
and Thalhimer (12) report its occurrence in cat's blood. 

The following is a brief abstract of the history of the patient 
in whose blood autoagglutination was observed : 

Case History. — Med. No. 38768. L. T.; 32 years; female. Rus- 
sian Jew. Married. Adm. Oct. 19, 1917. Discliarged Nov. 28. 
1917. Family and past history negative. One week before admis- 
sion the patient " caught cold," with fever, cough, dyspnea, palpita- 
tion, and pain in the right side of the chest. Physical examination 
on admission showed signs of a diffuse bronchopneumonia, and of 
mitral stenosis and insufficiency with auricular fibrillation. These 
findings were confirmed by X-ray and electrocardiographic exam- 
inations. Sputum culture showed both B. influenzae and Staphylo- 
coccus aureus. Blood culture and Wassermann reaction were 
negative. Urine normal, except for a trace of albumin, and, for a 
few days after admission, a trace of urobilin. The pulse ranged 
from 65 to 110; blood pressure from 100/.50 to 120/70. The tem- 
perature ranged from 100°-104°, gradually falling to normal four 
weeks after admission. The blood findings on admission were: 
red blood cells, 4,736,000; white blood cells, 9600; hemoglobin 
100 per cent. During the fever there was a polymorphonuclear 
leucocytosis of from 10,000 to 24,000. The hemoglobin fell to 
70 per cent and the red cells to 4,000,000 at the height of the 
infection, but rose to 90 per cent and 4.900,000 on discharge. 
Except for the count made on admission, it was impossible to make 
a red blood cell count during the febrile period on account of the 
autoagglutination, unless the solution were warmed. With recov- 
ery and return to normal temperature, warming above ordinary 
loom temperature was no longer necessary. The agglutinating 
activity of the serum then seemed to be somewhat feebler, and to 
require a lower temperature for its manifestation. We do not, 
however, attach very great significance to this observation for rea- 
sons which will be discussed later. 

The pheniiinciion of autnagglutinatidii was lirst noticed in 
our case on diluting the blood for a red cell count. Xew 
pipettes and new diluting fluids were used for a second count 
to eliminate the possibility that the agglutination was caused 
by dirty apparatus or improperly prepared solutions, but 
agglutination again occurred. It seemed obvious, then, that 
the peculiarity was inherent in the blood itself. 

In order to study this phenomenon, it was necessary to 
obtain serum, and unagglutinated red blood corpuscles free 
from serum. It occurred to us that agglutination might be 
prevented if the blood were kept warm, and the red cells washed 
several times in warm salt solution. It seemed inconceivable 
that the red blood cells were agglutinated in the circulating 
blood, and this suggested that the phenomenon might have 
been initiated at least by a lowering of the temperature of the 
blood. Also, by analosv with tlic hcniolvsin of inirnxysnnil 



ArniL, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



hemoglobinuria, which is fixed only at low temperatures, it 
seemed possible that fixation of the agglutinin might be avoided 
by washing the blood at body temperature. The observations 
of Landsteiner (7, 8) on the favoring effect of cold upon iso- 
and autoagglutination also suggested this method of obtaining 
unagglutinated red blood cells free from serum. 

Accordingly, 10 c. c. of blood were obtained by venajjunc- 
ture with a warm syringe. Five cubic centimeters of blood 
were allowed to clot in a test-tube to obtain serum, and the 
remaining 5 c. c. were added to 100 c. e. of sodium citrate 
solution warmed to 37° C. This mixture was immediately 
centrifugalized, and the cells washed twice in warm salt solu- 
tion, great care being taken to keep the temperature con- 
stantly at or near 37° C. No agglutination of the red lilooil 
cells occurred during the washing. 

A small amount of the original blood citrate mixture was 
kept separate, and allowed to stand at room temperature. In 
a few minutes marked agglutination became apparent maero- 
scopically and microscopically. After placing the mixture 
in the thermostat at 37° for a short time, the agglutinated 
clumps of red blood cells broke up. In a hanging drop prepa- 
ration the individual cells were seen to be perfectly preserved 
and evenly distributed throughout the suspension. This mix- 
ture was now placed in the ice-chest for a few minutes, and 
agglutination reappeared, and again disappeared entirely after 
warming to body temperature. This procedure was repeated 
.several times with the same result. 

A one per cent suspension of the washed red blood cells was 
then made in salt solution. Chilling this suspension caused 
no agglutination. The addition of a little of the patient's 
serum to part of the suspension, however, caused marked agglu- 
tination of the patient's red blood cells when the i^reparation 
was chilled. This agglutination, likewise, disappeared on 
warming to 37° C: 

From these experiments it seemed probable that the pecu- 
liarity of this blood was present in the serum and not in the 
red blood cells. In order to study the action of this serum on 
red blood cells from other individuals, and of other sera on 
the red cells of this individual, the group of the patient was 
determined by the method suggested by Moss (13). Micro- 
scopic preparations were made of the patient's serum with red 
blood cells from individuals of groups 2 and 3, and also of the 
patient's red cells with serum of groups 2 and 3. The follow- 
ing results were obtained : 

1. Group 2 serum -|- patient's red blood cells. Room tem- 
perature. One hour. Agglutination. This was not increased 
by chilling the mixture, nor were the clumps broken up by 
incubation at 37° C. 

2. Group 3 serum + patient's red blood cells. Room tem- 
perature. One hour. No agglutination either at room tem- 
perature or in the ice chest. 

3. Patient's serum -|- group 2 red blood cells. Room tem- 
perature. One hour. Agglutination similar to that in prepa- 
ration 1. 

4. Patient's serum + group 3 red blood cells. Room tem- 
perature. One hour. Slight agglutination at room tempera- 



ture, which became marked on chilling in the ice-chest, and 
which completely disappeared on warming to 37°. 

One could conclude, therefore, from these tests that the 
patient belonged to group 3. The agglutination occurring 
in preparation 4 differed from ordinary isoagglutination in its 
disappearance at 37°, and was evidently identical with tliat 
caused by the action of the patient's serum on her own red 
cells. In order to test this further, another preparation was 
set up with group 4 red blood cells. 

5. Patient's serum -|- group 4 red blood cells. Room tem- 
perature. One hour. Agglutination similar to that in test 4, 
disapiDearing completely on warming. 

It follows from these tests that there is no peculiarity in the 
patient's red blood cells to account for the autoagglutination. 
The patient's red blood cells were not agglutinated by the 
serum of another individual belonging to group 3, while the 
red blood cells of other individuals of groups 3 and 4 were also 
agglutinated in this peculiar way by the patient's serum. 

This serum, then, has two distinct types of agglutinating 
activity on human red blood cells, (1) the usual isoaggluti- 
nating activity manifested by sera from all individuals belong- 
ing to group 3 for cells from individuals of groups 1 and 2, 
(2) an agglutinating activity, manifested only at low tem- 
peratures for cells of the patient herself, and for cells of all 
individuals tested regardless of the blood group to which they 
belonged. 

The subslance causing the second type of agglutination must, 
therefore, be regarded as both an autoagglutinin and an iso- 
agglutinin. Furthermore, as will be shown later, this sub- 
stance has the power of agglutinating the red blood cells of 
various species of animals, and must, therefore, be a hetero- 
agglutinin as well. However, we shall follow the custom 
of using the term autoagglutination for this phenomenon to 
distinguish it from ordinary isoagglutination and heteroag- 
glutinatiou, bearing in mind, however, that it does not fully 
define the agglutinating activity of the serum. A more accu- 
rate term would perhaps be " cold agglutination." 

Fig. 1 shows the autoagglutination of the patient's cells 
by her own serum at room temperature. Fig. 2 shows the 
same preparation after warming. The clumps are nearly, but 
not entirely, broken up. Further warming would have resulted 
in complete separation of the cells. In preparations showing 
marked agglutination, the macroscopic and microscopic appear- 
ances are identical with those of cells agglutinated by an ordi- 
nary agglutinating serum. When the reaction is less marked, 
as in high dilutions of serum, or at temperatures only slightly 
reduced, the clumps are looser and the individual cells less 
distorted. In preparations showing minimal degrees of agglu- 
tination, the cells are simply assembled in small clusters, with- 
out heaping up of the cells or deforming of their outlines. No 
rouleaux formation was observed in the preparations. 

The properties of the patient's serum were then studied in 
the following ways : 

Progressively increasing dilutions of the serum were made 
(from 1-2 up to 1-4000). To 0.25 c. c. of each dilution was 
added an equal volume of a 1 per cent suspension of the 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 32 r. 



patient's red blood cells aud the mixtures placed in the ice- 
chest. At the end of 30 minutes agglutination was evident 
macroscopically in all dilutions of the serum up to and includ- 
ing 1-250, and after 24 hours also in 1-500. (These figures 
represent the final dilutions of the serum after the addition 
of the red blood cell suspension). This agglutinating sub- 
stance, then, was jDresent in the serum in high concentration. 
In order to determine the highest temperature at whicli 
agglutination was initiated, a similar series of tubes was set 
up. These tubes were then cooled bv immersion in a water 
bath, the temperature of which was gradually reduced. Agglu- 
tination was determined macroscopically. Tiie results are 
.shown in the following protocol : 

No agglutination. 



30° Half hour 

27° 

24° 

22° 

19^!° 

17° 
15° 
12° 



Agglutination in dilutions of serum up to 1-4. 
" •' " 1-S. 

' " 1-:J0. 

' " 1-30. 

" " 1-250. 

1-500. 



Ice chest over night. " " " " " 

A similar experiment with dilutions of serum to whicli were 
added red blood cells of an individual belonging to group 4 
gave identical results, indicating that the patient's cells were 
neither more nor less resistant to the agglutinating activity 
of Jier serum than were normal cells. Both sets when main- 
tained at 22° for three hours-showed agglutination in dilutions 
of- .scrum up to 1-60. Tlie critical tempi'rature, therefore. 
appeared to be about 22° C. 

The above set of tubes was then warmed gradually to see at 
wliat temperature the agglutination would disappear. Tlie 
following results were obtained : 
25° Half hour. Agglutination unchanged. 
30° 

34° " " partially broken up. 

34° One hour. " completely broken up. 

Tills e.xperinicnt indicated tbat agglutination persisted at a 
temperature higher than tiiat necessary for its initiation. 

In order to determiiu! the nature of this autoagglutiiiating 
substance in the serum, further tests were carried out. 

1. Heating tlie serum in 1-5 dilution at 60° for 1/2 jioiii- 
did not diminish its activity, while heating to 65° for 1/2 hom 
destroyed entirely its ability to cause agglutination of thr 
patient's red blood cells. 

2. Dialyzing the serum in ((illodion sacs against physiologi- 
cal salt .solution for 21 hours did not impair its agglutinating: 
ability. 

3. Extraction of the scrniii with cblorol'orni did not renui\c 
these agglutinins. 

4. Preci]iitation oi' the globulins from the serum by am- 
monium sulphate resulted in disajjpearance of the agglutinin 
from the serum. First the " euglobulin " was precipitated by 
the addition of 36 volumes per cent of a saturated solution of 
ammonium sulphate. The precipitate was washed in .36 per 
cent saturated solution of ammonium sulphate, and dis.solved 
in physiological salt solution. Tlic ammonium sulphate was 



then removed by dialysis. This euglobulin solution caused 
marked agglutination of the patient's washed red blood cells 
in the cold, like that produced by untreated serum. The 
" pseudoglobulin " was next precipitated from the serum by 
the addition of saturated ammonium sulphate solution to a con- 
centration of 44 volumes per cent. The precipitate was then 
washed with 44 per cent saturated solution of ammonium sul- 
phate, filtered, dissolved in physiological salt solution, and 
dialyzed. This pseudoglobulin solution caused no agglutina- 
tion of the patient's red blood cells. The serum from which 
euglobulin and pseudoglobulin had been precipitated was 
dialyzed to remove the ammonium sulphate, aud tested with 
the patient's red blood cells. Xo agglutination occurred. It 
was clear, then, that this autoagglutinin was associated with 
the " euglobulin " of the scrum, as has been demonstrated in 
connection with iso- aud other agglutinins. 

Further work on the nature of the agglutinin was done in 
connection with absorption experiments, and will be discussed 
with them in a later paragraph. 

The serum of the patient was tested for the presence of an 
autohemolysin analogous to that occurring in the serum of 
patients with jjaroxysmal hemoglobinuria. As shown by 
Donath and Landsteiner (14) and others, the serum from these 
patients contains an autohemolysin which combines with tlie 
red blood cells only at low temperatures, and hemolyzes them 
on subsequent raising of the temperature. If a suspension of 
red blood cells is added to such a serum, aud the mixture is 
fir.st chilled and then incubated at 37°, hemolysis takes place, 
whereas no hemolysis occurs if the preparation is incubated 
without previous chilling. 

The following preparations were set up. tubes 2 and 3 being 
control tests: 

1. Patient's serum 0.25 c. c. -1- patienfs corpuscles 0.25 c. c. (1% 

suspension) 0° C. 1 hour, 37° C. 2 hours. 

2. Salt solution 0.25 c. c. -|- patient's corpuscles 0.25 c. c. (1% 

suspension) 0° C. 1 hour, 37° C. 2 hours. 

3. Patient's serum 0.25 c.c. -|- patient's corpuscles 0.25 c. c. (1% 

suspension) 37° 2 hours. 

Xo hemolysis occurred in the test or in any of the control 
pie]iarations. Even after standing in the ice-chest over night 
there was no hemolysis, though autoagglutination was evident. 
It was thought, then, that an autohemolysLii might still be 
present, but its action on the red blood cells might be prevented 
by a lack ot the necessary amount of complement, as was 
the case in the henioglobinuric sera studied by Jleyer and 
I'hnmerich (15). Accordingly, a similar series was .set up with 
O.l e. c. of guinea-pig serum added to each tube. Xo hemolysis 
ri'sulted. It seemed obvious, then, that the absence of hemolysis 
in the first experiment was not due to a lack of complement, 
and that probably no autohemolysin was present. In vivo 
experiments to demonstrate autohemolysis were not tried on 
account of the theoretical danger of causing intravascular 
agglutination. 

Attempts were made to absorb out the autoagglutinin from 
the serum by digesting it with the homolo,irous red blood cells, 
and interesting results were obtained. In the first experiment. 



April, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



89 



the digestion was carried out at 37° C. after an initial cliilliui;'. 
and in the second experiment at about 3° to 5° C. 

1 . Warm digestion. To 0.5 c. c. of the patient's serum were 
added 2.5 c. c. of a 10 per cent suspension of the patient's red 
blood cells. Tliis mixture was kept at 3° ('. for half an hour. 
Autoagglutination became very marked. The mixture was then 
•warmed to 37° C. with resulting disappearance of the agglu- 
tination. The red cells were centrifugalized out. washed twice 
with warm salt solution, and suspended in salt solution. Chill- 
ing this suspension caused no agglutination, and hence tlie 
autoagglutinin had not been fixed, or remained fixed to the 
cells. The activity of the supernatant serum was tested l>y 
tlie addition of fresh red cells. Agglutination became marked 
<iu chilling this preparation. Therefore, the autoagglutinin 
was still present in the digested serum. The suj)ernatant serum 
was again digested with the patient's red blood cells in the 
same way. These red cells were washed in warm salt solution, 
and the absence of any agglutinin fixed to the cells was demon- 
strated by their failure to become agglutinated on chilling 
them. The autoagglutinin was again demonstrable in the 
serum. One must conclude, therefore, that the autoagglutinin 
is not fixed to the bells, but remains free in the serum, when 
the digestion is carried out at body temperature. 

3. Cold digestion. To 0.5 c. c. of the patient's serum were 
added 2.5 c. c. of a 10 per cent suspension of the patient's 
Ted blood cells. This mixture was kept at 3° C, and not allowed 
to become warm. Agglutination was marked throughout the 
experiment. The agglutinated red cells were centrifugalized 
out, and the supernatant serum tested for autoagglutinin. A 
preparation of this serum with fresh washed red blood cells 
showed no agglutination after prolonged chilling. Digestion 
with the homologous red cells in the cold had therefore absorbed 
the autoagglutinins completely from the serum. The sedi- 
mented red blood cells were washed twice w'ith cold salt solu- 
tion, and suspended in warm salt solution. The agglutina- 
tion, which had been marked, disappeared in the warm solu- 
tion, but reappeared on chilling this suspension again. The 
autoagglutinin, then, had not been removed from the cells by 
the cold washings. This suspension was warmed again, centrif- 
ugalized, and the supernatant fluid tested to see if the auto- 
agglutinin had been liberated from the red cells on heating. 
This was found to be the case. The supernatant salt solution 
caused typical agglutination of fresh red blood cells in tlie 
cold. This solution did not cause agglutination of group 2 
cells, nor of animal cells at 37°, and therefore did not contain 
normal isoagglutinin or heteroagglutinins. It contained the 
autoagglutinin isolated in purified form, and made possible 
a study of its activity undisturbed by other agglutinating sub- 
stances in the serum. The sedimented red blood cells were 
washed twice with warm salt solution, and a suspension of them 
was chilled. No agglutination occurred, showing that the 
autoagglutinin had been entirely liberated from the red blood 
cells by warming. 

By these experiments, therefore, it was shown that tlie 
autoagglutinin was not absorbed from the serum by digestion 
with red blood cells if the mixture were kept warm. If, Imw - 



ever, digestion were carried out in the cold, the autoagglutinin 
was removed from the serum and fixed to the red blood cells. 
The physical or chemical process involved in the union was. 
however, a reversible one, and caused no permanent change in 
the red blood cells, since the autoagglutinin could be entirely 
liberated from the red blood cells by warming them, and since 
these red blood cells were now agglutinable by fresh serum. 

These warm and cold absorption experiments were repeated, 
digesting the patient's serum with cells from an individual 
belonging to group 4. Exactly the same results were obtained. 
Eemoving the autoagglutinin for the patient's cells by cold 
digestion removed also that for group 4 cells, and vice versa. 

The patient's serum from which the autoagglutinin had 
been absorbed was then tested to see if the ordinary normal 
isoagglutinin for group 2 cells had been removed also. This 
was found not to be the case. The absorbed serum caused 
marked agglutination of group 2 cells at 37° C, which was not 
increased by chilling. The isoagglutinin liad not been affected 
by absorption of the autoagglutinin. 

The isoagglutinin for group 2 cells was then absorbed from 
the patient's serum. Digestion of 0.5 c. c. of the serum with 
0.1 c. e. of group 2 red blood cell " mush " at 37° for half an 
hour, absorbed completely the isoagglutinin. A preparation of 
this absorbed .serum with fresh group 2 cells showed no agglu- 
tination when kept in the thermostat. However, when this 
preparation was placed in the ice-chest, a marked agglutination 
occurred, which disappeared on warming. This absorbed 
serum also agglutinated the patient's red blood cells, and 
cells from other individuals of groups 3 and 4, on chilling, with 
disappearance of the agglutination on warming. In this ex- 
periment, therefore, it was shown that the isoagglutinin for 
group 2 cells could be absorljed independently of the autoagglu- 
tinin, and that red blood cells of group 2, like those of groups 
3 and 4, were susceptible to the action of the " cold '' or " auto- 
agglutinin." 

It was also possible to demonstrate that the patient's serum 
possessed the property of causing " cold " agglutination of the 
red blood cells of other animals, in addition to ordinary hetero- 
agglutination, and that the agglutination of these cells was 
brought about by the same substance which was active on 
human cells. This could be shown very easily with hen's cells, 
since no heteroagglutinins were present in the serum against 
the blood of the two hens used. Mixtures of this serum with 
washed hen's cells showed no agglutination at thermostat tem- 
perature, but marked agglutination at ice-box temperature. 
This agglutination broke up on warming the mixture, exactly 
as did the autoagglutination of human cells, and reformed on 
subsequent cooling. 

Tests were also made with sheep, guinea-pig. rabbit, pig, 
and cat red blood cells. Heteroagglutinins were present in the 
serum for these species of cells. At first it was thought that 
these might be eliminated by using progressively increasing 
dilutions of serum for the tests, since the autoagglutinin, 
though much feebler than in the first experiments, was still 
present in fairly high concentration (about 1-100). The fol- 
lowing tests wore set up to determine the titer of the hetero- 



90 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 32G 



agglutinins for these cells. After incubating at 37° for one 
hour, the degree of agglutination was noted, and the prepara- 
tions were then chilled, and a second observation made. The 
following results were obtained : 

Dilutions of patient's Final serum ,,,..,,. ,-« 

serum + sheep cells dilution 3i 1 hr. Cliilled Ji 

MO 1-20 + + + ++++ + + + + 

1-20 1-40 + +++ 

1-40 1-SO ± 

1-SO 1160 

Dilutions of patient's Final serum 

serum J- guinea-pig cells dilution 37" 1 hr. Chilled -ii 

1-10 1-20 + + + + 

1-20 1-40 + + + 

1-40 1-J>0 -f 

1-80 1-160 

Dilutions of patient's Final serum 

serum + rabbit cells dilution 37° 1 hr. thillc-d 3. 

MO 1-20 + + -+-+ + + + + + + + + 

1-20 1-40 +++ + + + + + + + + 

1-40 1-80 ++ + + + + + 

1-80 1-160 + + + + + 

In tlie test witli sheep cells, a dilution of serum of 1-20 
sufficed to eliminate heteroagglutination. The " autoagglu- 
tinating" activity of the serum on sheep cells could then be 
demonstrated by chilling this mixture. This was better shown 
with the guinea-pig cells.. Serum diluted 1-10 caused no 
heteroagglutination of the guinea-pig cells, while " autoagglu- 
tination " occurred with serum diluted up to 1-40. The results 
with the rabbit red blood cells are less definite, since hetero- 
agglutination was present even with the serum diluted 1-80. 

More conclusive results were obtained by digesting the 
patient's serum at 37° C. with sheep, guinea-pig, cat, pig, and 
rabbit red blood cells to remove the heteroagglutinins for these 
cells. 

The patient's scrum was iligcsteil with slieep cells (0.5 v. v. 
serum -|- 0.3 c. e. siieep cell ''mush") at 37° for one hour. 
The cells were then removed by centrifugalization, and fresh 
sheep cells added. No agglutination occurred at 37°, showing 
that the absorption of heteroagglutinin was complete. On cool- 
ing this mixture, agglutination became marked, and on warm- 
ing again it broke up exactly as did the autoagglutinatioii of 
the patient's cells. 

Heteroagglutinins for guinea-pig, cat, and pig cells were 
removed in the same way, and the activity of the "autoagglu- 
tiiiin " (in these cells could then be demonstrated. 

Heteroagglutinin for rabbit cells was also removed from the 
serum by digesting 0.5 c. c. of serum with 0.2 c. c. rabbit cell 
" mush " at 37° C. A preparation of this absorbed serum with 
fresh rabbit cells showed no agglutination at body temperature, 
but marked agglutination at ice-box temperature, which could 
be broken up on warming. That is to say, the heteroagglutinin 
was absorbed, leaving the autoagglutinin, which was active on 
rabbit cells. The absorbed serum was shown to still possess the 
autoagglutinating activity on group 4 red blood cells. Mix- 
tures of this serum with guinea-pig cells and with sheep cells 
showed agglutination at 37°, demonstratin<r that tlie hetem- 



agglutiuins for these cells had not been affected by removing^ 
the heteroagglutinin for rabbit cells. It was further shown 
that this absorbed serum also contained the isoagglutinin for 
group 2 cells. 

Ve then tried to absorb the autoagglutinin from this serum 
from which- the heteroagglutinin for rabbit cells had been 
removed, by digesting it with 0.3 c. c. rabbit cell mush at ice-- 
box temperature. The agglutinated cells were then removed 
by centrifugalization in the cold, and fresh rabbit cells were 
added to test the completeness of the absorption. Agglutina- 
tion occurred when the mixture was chilled, showing that the 
serum was not exhausted. Three further digestions, each with 
0.2 c. c. of rabbit cell mush, were necessary before absorption 
of the autoagglutinin was complete. We then tested the agglu- 
tinating activity of the serum for human group 4 red blood 
cells. Cooling this mixture caused no agglutination. There- 
fore, removal of the " autoagglutinin " for rabbit cells had 
also removed the " autoagglutinin " for human cells. That 
this disappearance of agglutinin was the result of a specifir 
agglutinin absorption and not merely a non-specific mechanical 
removal by the relatively large quantity of cells used in tlie 
digestion, is indicated by the fact that the exhausted serum 
still retained, practically undiminished, its heteroagglutinins 
for guinea-pig and sheep cells, and its isoagglutinin for group 3 
human cells. It seems probable, therefore, that the same sub- 
stance was responsible for the " autoagglutination " of both 
rabbit and human cells. 

The action of the autoagglutinin on the cells from different 
species of animals was also studied by means of the "puri- 
fied agglutinin " already described. The autoagglutinin was 
absorbed from the serum by digestion in the cold with group 
4 human red blood cells, and after washing the cells in cold 
salt solution several times, the autoagglutinin was liberated 
in warm salt solution. A solution of purified agglutinin was 
also prepared by absorbing it from the serum in the same way 
with rabbit cells. These solutions containing purified agglu- 
tinin were tested with rabbit, sheep, and guinea-pig red blood 
cells, and with human red blood cells of groups 2 and 4. No 
agglutination occurred in any of the mixtures at 37°. Agglu- 
tination became evident, however, in all of the preparations 
upon chiUing, and disappeared upon warming them. These 
purified autoagglutinin solutions, then, contained no hotero- 
or isoagglutinin, as far as tested, but only the autoagglutinin 
which was shown to be active on all the species of red blootl 
cells tested. This purified autoagglutinin, isolated by diges- 
tion of the serum with human red blood cells, was identical in 
its behavior with that obtained by means of animal (rabbit) 
red blood cells. One must conclude, therefore, that the auto- 
agglutinin is a single substance, whicli, unlike iso- and hetero- 
agglutinins is not specific, but is active on the red blood cells 
of different species of animals. 

The action of the autoagglutinin was next tested on cells 
other than blood cells. An emulsion of epithelial cells from 
the urinary tract was prepared by ccntrifugalizing normal 
urine. As would be expected, the patient's serum did not cause 
anv airfrhitination of these cells at 0° or at 37° C. 



April, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



91 



We attempted to study the chemical nature of the autoagglu- 
tinin, and particularly to determine whether or not it could 
1)0 freed from proteid. The results obtained so far are incon- 
clusive on account of the small amount of serum available. "We 
found that, like other agghitinins, it was precipitated from 
the serum with the "euglobulin" fraction of the proteid by 
the addition. of 36 volumes per cent of a saturated solution of 
ammonium sulphate. The fact that the agglutinated red blood 
cells, after being washed free from serum with cold salt solu- 
tion, give up the agglutinin on warming, suggested that this 
method might be used to obtain the active substance in a rela- 
tively pure form, free from the ordinary proteid constituents 
of the serum. 

Landsteiner and Jagic (16) have used a similar method in 
the study of the heteroagglutinin for goose red blood cells 
in beef serum. They found that this agglutinin is best 
absorbed in the cold, and is partially liberated on heating to 
.jO° C. They digested a large volume of beef serum with 
thoroughly washed goose cell stroma in the cold, washed the 
agglutinated stroma in the cold, then suspended it in salt 
solution, and liberated the agglutinin by heating. This solu- 
tion contained 0.2 per cent proteid, as compared with 6.6 per 
cent in the original serum. The agglutinin was precipitated 
from this solution with ammonimn suli^hate. However, the 
solution still contained considerable proteid independent of 
agglutinin, since most of the agglutinin could be removed by 
the addition of fresh stroma, leaving behind in the solution 
most of the substances giving the tests for proteid. They did 
not attempt further purification by repeating the procedure. 

In making the tests for proteid, we used Heller's nitric acid 
test, since it was found to be much more sensitive for the pro- 
teids of serum than were the ordinary color reactions. Prelimi- 
nary tests showed that normal horse serum in 1-2000 dilution 
gave a positive reaction with Heller's test, whereas Millon's 
and the biuret reaction were positive only in concentrations of 
1-125, or higher. 

Presli red blood cells were used at first in the test but were 
found to be unsatisfactory. They could easily be washed free 
from serum, but after agglutination the mechanical injury 
incurred during the washings, together with the repeated 
warming and chilling, caused slight hemolysis, with liberation 
of sufficient hemoglobin to give a positive Heller's test. Xo 
better results were obtained by using red blood cells fi.xed in 
1/2 per cent formalin. These cells absorbed agglutinin from 
the serum exactly as did fresh red blood cells. The different 
manipulations, however, caused some hemolysis of these cells 
also. 

More satisfactory results were obtained by using stroma pre- 
pared by laking red blood cells belonging to group 4 with 
distilled water, and washing this red blood cell stroma several 
times. These laked red blood cells absorbed agglutinin from 
the serum in the cold, became agglutinated, and gave up 
agglutinin when warmed, with disappearance of agglutination. 
exactly as did fresh red blood cells. To 0.25 c. c. of thoroughly 
washed stroma was added 0.5 c. c. of the patient's serum. 
This was chilled in ice water half an hour. Macroscopic floc- 



culi became visible in the suspension. After centrifugalizing 
cold the supernatant serum was pipetted off, and the .stroma 
suspended in warm salt solution, in order to break \vp the 
clumps and to permit thorough washing. After the clumps 
were broken up the mixture was again chilled and centrifugal- 
ized. The supernatant salt solution was tested for proteid by 
Heller's test. After this had been repeated three times, the 
supernatant salt solution no longer gave a positive Heller's test. 
The stroma was then suspended in salt solution, and warmed 
to liberate the autoagglutinin, and the salt solution was cen- 
trifugalized free from stroma. This solution was shown to 
contain autoagglutinin by testing it with fresh group 4 cells, 
though the activity of the solution was not as marked as that of 
the original serum, and had evidently been weakened by the 
repeated manipulations. Heller's test was negative with this 
agglutinin solution, and the addition of ammonium sulphate 
to it caused no visible precipitate. By this method, therefore, 
we were able to obtain an agglutinating solution which gave 
a negative Heller's test, and hence contained less proteid than 
is contained in a 1-2000 dilution of serum. Though these 
results are suggestive, we cannot conclude definitely that this 
agglutinin is not a proteid, since the limited quantity of serum 
available did not permit of further tests. 

In order to differentiate this autoagglutination more clearly 
from rouleaux formation, a similar study was made of this 
phenomenon. This work is still incomplete, and a more 
detailed report of it will appear in a later paper. Certain 
differences in these two phenomena may be mentioned here. 
As pointed out by Decastello and Sturli (17), and by Sellards 
(3), and confirmed in our experiments, serum is able to cause 
rouleaux formation only in high concentrations. In the sera 
which we studied, a dilution of 1-4 was sufficient to destroy 
this activity. The autoagglutinating serum, on the other hand, 
was active after dilution to 1-500. These authors also point 
out that the property of the serum of stimulating rouleaux 
formation, and that of the red blood cells of becoming clumped 
in rouleaus is very imstable, and disappears within a few hours, 
or, at most, a few days. This was true in our experiments 
with rouleaux-forming serum, while the serum causing auto- 
agglutination has remained active, with but slight diminution 
in strength, for several months. Fresh cells were not necessary 
for demonstrating autoagglutination. Heating the rouleaux- 
forming serum to 65° for 1/2 hour increased definitely its 
activity, as noted by Sellards (3), while heating the autoagglu- 
tinating serum to this point entirely destroyed its activity. 

In our experiments, the formation of rouleaux seemed not 
to be affected by raising or lowering the temperature of the 
mixture, as was the agglutination of red blood cells by the auto- 
agglutinating serum. After preparations showing rouleaux 
formation had stood at room temperature for several hours, 
the rouleaux broke up much as did the clumps of autoagglu- 
tinated red blood cells. This breaking up of rouleaux, how- 
ever, occurred at low temperatures as well as at body tempera- 
ture and, after it once occurred, no reformation of the rouleaux 
could be obtained. We found that the rouleaux stimulating 
substance could not be absorbed from the serum even by 



92 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 326 



repeated digestions with large quantities of red blood cells, 
whereas the autoagglutinin could readily be alisorbed. Certain 
jjoints of resemblance between these two active substances were 
Ijrought out in our studies. Both were active on cells from 
other individuals. Both substances were precipitated from the 
serum with the " eugloliulin "' by the addition of 36 volumes 
per cent of saturated ammonium sulphate solution. Both sub- 
stances remained in the serum after dialysis in a collodion sac. 
However, in the case of the rouleaux-forming serum, dialysis 
could only be carried out for 24 hours, because the activity 
of this serum di.«appeared on longer standing. From these 
observations it .seems clear that autoagglutination and rouleaux 
formation are entirely different phenomeua. 

DISCUSSION 

The question then came up, is the phenomenon of autoagglu- 
tination in this patient's blood in any way related to the disease 
for which she entered the hospital? To settle this point, we 
studied the blood again during convalescence, shortly before her 
discliarge from the hospital. Red blood cell counts could then 
be made without using warm solutions. Eed blood cells and 
serum were obtained as before. Progressive dilutions of serum 
were made as previously and red blood cells added. Agglutina- 
tion occurred only in dilutions under 1-16, and only at temper- 
atures below 11° C. To again test out this point, other speci- 
mens of serum and red blood cells were obtained two months 
after the patient had recovered from her pneumonia. This 
time care was taken to keep the blood warm while it was 
clotting, and until the serum was removed, to prevent any 
fixation of the autoagglutinin to the cells in the clot, with 
resulting reduction in the strength of the serum. Autoagglu- 
tination again occurred in dilutions up to 1-16, and at tem- 
peratures below 15° C. At this time a iVw drops of blood 
were obtained from a daughter of tlie |)atient, and a similar 
autoagglutinin was found in this blood. It appeared to be 
somewhat feebler than that present in the mother's sermu, but 
the anu)unt of blood obtained was. insutlieient for further tests. 
It is obvious, therefore, that this peculiarity was quite inde- 
pendent of the disease from which the patient was suffering. 
and was an individual peculiarity, apparently liereditary. The 
increased strength of tlie agglutinin during the early part of 
her disease may liaxc liren related in sonic way to the infection, 
or may have bi'cii purely accidental. 

SUMMARY 

Autoagglutination, or agglutination of red blood cells by 
serum from the same individual, was observed in the blood of 
a patient admitted to the hospital on account of a broncho- 
pneumonia associated with chronic mitral endocarditis. 

Agglutination occnrrcd only at low temperatures (below 
22° C), and broke up if heated to body temperature. Agglu- 
tination could be reproduced by again chilling the same prepa- 
ration. 

This serum caused similnr agglutination of rinl blood cells 
from other individuals of the same blood group (group 3), and 



also of group -1. (It contained ordinary isoagglutiuins active 
at body temperature for cells of members of groups 1 and 2.) 
The cells of the patient washed free from serum showed no 
tendency to agglutination, and behaved exactly as did cells 
from other individuals of group 3. Hence the phenomenon 
depended solely on a peculiarity of the serum, and not of the 
cells. 

The active substance in the serum had many of the prop- 
erties of an ordinary agglutinin. It was active in fairly high 
dilution (up to 1-500). It resisted heating to 60° C. for 
1/2 hour, but was destroyed at 65° C. It remained active 
after preservation in the ice-box for several months. It was 
not dialyzable. It was not removed by extraction with chloro- 
form. It was precipitated with the "euglobulin" by 36 vol- 
umes per cent of saturated ammonium sulphate solution. It 
was absorbed from the serum during the process of agglutina- 
tion (at low temperatures). 

It was entirely distinct from the ordinary isoagglutinins in 
the serum, since either one could be removed from the serum, 
leaving the other intact. 

The autoagglutinin differed from ordinary agglutinins in the 
following ways : 1. It was active only at low temperature, the 
agglutination breaking up on warming. 2. It was absorbed 
from the serum only at low temperature, and was liberated 
from the cells on warming. 3. It was active on red blood cells 
from all of the different species of animals with which it was 
tested (man, rabbit, guinea-pig, hen. sheep, cat. and pig). 
That the same substance was concerned in the agglutination of 
human cells and of cells from these different animals, and that 
it was distinct from the ordinary heteroagglutinins, which 
were also present in the serum, was shown by the absor])tion 
tests already described. 

An attempt was made to study the chemical nature of the 
autoagglutinin, especially its relation to proteid, but the results 
were inconclusive. By liberating the agglutinin from washed, 
agglutinated red blood cell stroma in warm salt solution, a 
solution of agglutinin was obtained which gave a negative 
Heller's test and showed no precipitate on the addition of 
ammonium sulphate. This solution, therefore, contained less 
proteid than is contained in a 1-2000 dilution of horse serum. 
Further tests were impossible on account of the small supply 
of serum available, and the weakening of the autoagglutinin 
caused by the manipulations. 

No autohemolysin was juvsent in the soi'uni. 

A similar study of rouleaux formation was made in order 
to differentiate it more clearly from autoagglutiiuition. The 
substance causing rouleaux formation resembled the autoagglu- 
tinin in that it, also, was active on cells from other individuals. 
Both substances were precipitated from the serum with the 
" euglobulin,"' and neither was dialyzable. Unlike the autoag- 
glutinin, the rouleaux-forming substance Avas active only in 
concentrated serum. Its activity rapidly disapjieared upon 
standing, and fresh cells were necessary for the fornuition of 
rouleaux. Kouleaux formation occurred equally well at high 
or low temperatures. Heating the serum to 65° C. increased 
its rouleaux-l'orminu' iiower. This sid)stance was not absorbed 



April, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



93 



s\h 



the 



ml.: 



from the scrum liy the 
formation. 

The presence of the autoagglutinin was probahly not related 
in any way to the disease from which the patient was suft'erinp;. 
It persisted with slight variation in strength for a period of 
two months' observation, and was found to be present in the 
serum of a daughter of the patient. Hence it was probably not 
a pathological phenomenon, but an individual, hereditary 
peculiarity. 

REFERENCES 

1. Minot, G. R.: Methods for testing donors for transfusion of 
blood, and consideration of factors influencing agglutination and 
hemolysis. Boston M. and S. J., 1916, CLXXIV, 667-674, 

2. Fishbein, M.: Isoagglutination in man and lower animals. 
J. Infect. Dis., 1913, XII, 133-139. 

3. Sellards, A. W. : The effect of heated serum on rouleaux 
formation of red blood corpuscles. Bull. Johns Hopkins Hosp.. 
1908, XIX, 271-274. 

4. Reitmann, A.: Ueber Bluterbrechen bei Lebercirrhose. Wien. 
klin. Wchnschr., 1S90, III, 404-407. 

5. Ascoli. M. : Isoagglutinine und Isolysine menschlicher Blut- 
sera. Miinch. med. Wchnschr., 1901, XLVIII, 1239-1241. 

6. Klein, A.: Beitrage zur Kenntnis der Agglutination rother 
Blutkbrperchen. Wien. klin. Wchnschr., 1902, XV, 413-418. 



7. Landsteiner, K.: Ueber Beziehungen zwischen dem Blut- 
serum und den Korperzellen. Miinch. med. Wchnschr., 1903, L, 
1812-1814. 

8. Landsteiner, K.: Ueber Serumagglutinine. Miinch. med. 
Wchnschr., 1902, XLIX, 1905-1908. 

9. Hektoen, L.: Phagocytosis of red corpuscles. J. Infect. Dis., 
1906, III, 721-730. 

10. Hektoen, L. : Isoagglutination of human corpuscles. J. 
Infect. Dis., 1907, IV., 297-303. 

11. Rous, P.: Personal communication. 

12. Ottenberg, R., and Thalhimer, W. : Studies In experimental 
transfusion. J. Med. Research, 1915, XXXIII, 213-229. 

13. Moss, W. L. : A simplified method for determining the iso- 
agglutinln group in the selection of donors for blood transfusion. 
J. Am. M. Ass,, 1917, LXVIII, 1905-1906. 

14. Donath, J., and Landsteiner, K.: Ueber paroxysmale Hamo- 
globinurie. Munch, med. Wchnschr., 1904, LI, 1590-1598. 

15. Meyer, E., and Emmerich, E.: Ueber paroxysmale Hamo- 
globinurie. Deutsches Arch. f. klin. Med., 1909, XCVI, 287-327. 

16. Landsteiner. K., and Jagic, N.: Ueber die Verbindungen und 
die Entstehung von Immunkorpern. Miinch. med. Wchnschr., 
1903, L, 764-768. 

17. Decastello, A. v., and Sturli, A.: Ueber die Isoagglutinine im 
Serum gesunder und kranker Menschen. Miinch. med. Wchnschr., 
1902, XLIX, 1090-1095. 



A SIMPLE METHOD FOR THE DETERMINATION OF 
VENOUS PRESSURE 

By N. WoETii Brownt, il. D. 
(From the Medical Clinic of The Johns Hopkins Hospital) 



A convenient instrument for the measurement of pressure 
within peripheral veins may be easily constructed from an 
ordinary mercurial manometer. The apparatus consists of a 
single-limb manometer in which water, carbon tetrachloride 
(Carbona) (Sj). Gr. 1.5) or bromoform (Sp. Gr. 2.5) is sub- 
stituted for mercury. To the manometer is connected a small, 
saddle-shaped cup, 2 cm, in diameter, covered with the thinnest 
rubber tissue obtainable. This membrane must be loosely 
applied and should permit free oscillation without tension. A 
rubber bulb with thumb-screw compressor regulates the pres- 
sure within the manometer. The use of carbona or bromoform 
instead of water is advocated because of higher specific gravity 
and lower viscosity, Carbona is preferred for routine observa- 
tions. The readings are easily reduced to water pressure. 

The principle employed is tliat described by von Basch in 
18T6 for the determination of arterial pressure.' Oliver' and 
SewalP have published studies on venous pressure obtained in 
a somewhat similar manner but using a spring jjressure gauge 
applied directly over the vein. The manometer devised and 
used by Hooker ' and later by Clark ' has been used for sonic 
time in this institution and the observations made with it have 
demonstrated the value of venous pressure estimations in the 
clinical study of cardio-vascular and pulmonary disease. 



' Presented before The Johns Hopkins Medical Society, May 21, 
1917. 



The method here described differs from that used in record- 
ing venous pressures with the Hooker manometer. With the 




Venous Pressure Apparatus. 



latter, a glass cup is cemented to the skin and the pressure 
necessary to obliterate the vein is determined by direct inspec- 
tion through the cup, of the collapsed vessel ; in this, the pres- 



94 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 32G 



^^ure required to prevent the return flow is measured and the 
appearance of a venous " wave " marks the reading point. It 
is desirable to use a prominent superficial vein in which the 
valves are effective. Pressure in the manometer is raised sev- 
eral centimeters and the cup, or capsule, is placed upon the 
vein with sufficient pressure to obstruct the return flow. The 
vein on the proximal side of the capsule is emptied by stroking 
in the direction of venous flow. The pressure in the mano- 
meter is allowed to fall by opening the needle valve. When the 
venous pressure equals the manometer pressure the vein above 
the capsule will rapidly fill. A reading at this time will give 
tlie approximate venous pressure. 




/\ 



— ^ — 

Fig. 2. — (a) Before pressure is applied. Pressure in the vein 
is greater than within the capsule. 

(b) Capsule pressed downward. Lumen of the vein obliterated. 
Pressure in the capsule is greater than in the vein. 

(c) Capsule is slowly raised. When the pressure in the vein 
oquals that within the capsule, blood will pass through the partly 
compre.ssed vessel. The manometer reading at this point indicates 
tlie venous pressure. 

After thi.< ])reliiiiiuary oliservation the capsule is iuUated but 
not distended (0.5 cm. water j^ressure) and the manometer 
valves arc clo.scd. ' The capsule and manometer now form a 
closed circuit. Eepeated readings can be made by pressing 
down the capsule, stripping the vein and slowly raising the 
capsule, observing the height of the column in the manometer 
when the venous flow first returns. If reasonable care is exer- 
cised, the variations should not exceed one centimeter. 
Mechanical factors, which may under certain conditions influ- 
ence results thus obtained, are constant and so insignificant 
that for clinical purposes they may be disregarded. It is 
important that the capsule be so adjusted that its margin does 
not compress the vein. As with all methods of estimating 
venous pressure the vein employed must l)e at tlie heart level. 



For the fluid manometer may be substituted an aneroid ad- 
justed to record low pressures in centimeters of water. 

Simultaneous observations made with Hooker's venous 
manometer and with this apparatus give approximately the 
same results. Xormal pressures, so far observed, when taken 
upon individuals resting quietly in the recumbent position 
with the arm extended and the hand at the heart level give 
readings between 3 and 9 cm. H,0. Two cases of essential 
hypertension had pressures within normal limits. A well com- 
pensated aortic stenosis showed an average of 8.1 cm. Two 
patients with valvular lesions and atiricular fibrillation had 
venous pressures ranging from 12 to 18 cm. of water. An 
uncompensated aortic regurgitation during the periods of dysp- 
noea showed a pressure of 26 cm. A patient with obstruction 
in the superior vena cava gave a peripheral pressure of 1 t.G 
cm., while the thoracic, at the same level, serving as a col- 
lateral, showed a pressure of 12.7 cm. Thrombosis of the left 
subclavian vein produced a pressure of 30 cm. in the left hand, 
whereas on the unaffected side it measured only 16 cm. 

From these limited observations we are led to believe that 
readings with this instrument of 10 cm., or lower, represent 
normal venous pressures. In cardiac lesions pressures between 
12 and 18 cm. suggest moderate decompensation, whereas con- 
stant pressures of from 20 to 30 cm., or over, indicate venous 
stasis and serious myocardial insufficiency. 

The advantages of the method described are obvious. The 
determinations are equal in accuracy to any method except that 
which depends upon the introduction of a canula. The sim- 
plicity of the apparatus, its ease of manipulation, the rapidity 
with which observations can be made and an unmistakable 
reading-point, will commend its tise for clinical purposes. 

REFERE^-CES 

1. Janeway: The Clinical Study of Blood Pressure, 1904, p. 43. 

2. Oliver: Am. Jour. Physiol., 189S, XXII, 51; Am. Jour. Physiol., 
1S9S, XXIII, 5. 

3. Sewall: Jour. Am. Med. Assn., 1906. XLVII, p. 1279. 

4. Hooker and Eyster: Johns Hopkins Hosp. Bull., 190S, XIX, 
p. 274. Hooker: Am. Jour. Physiol.. 1911, XXVIII, 5, p. 235; 
Am. Jour. Physiol., 1914, XXXV. 1, p. 7:^; Am. Jour. Physiol., 1916, 
XL, 1, p. 43. 

5. Clark: Arch. Int. Med., 1915. XVI. p. 587. 



ABSTRACTS OF PAPERS 



Representing Work Done in The Johns Hopkins Hospital, but Published or to be Published Elsewhere than in the Bulletin. 

Prepared by the Authors. 



THE MAINTENANCE DIET IN DIABETES MELLITUS AS 

DETERMINED BY THE NITROGEN EQUILIBRIUM 

By Hkum.vn 0. Mosknthai. and S.v:vuti:l W. Clauskx 

(From the Medical Clinic of The Johns Hoi)kins Hospital) 

In the treatment of diabetes mellitus, there are two guiding 

]irinciples which determine the caloric value of the diet. In 

the first place, the quantity of carbohydrates, proteins and fats 

ottered the patient must be within his carbohydrate tolerance; 

that is, the diet must be so regulated that the urine remains 



^ui;ar-f rcc. It is generally acknowledged that under these cir- 
cumstances the disease itself is treated in the most effective 
manner. Secondly, a diet of sufficient caloric value should be 
offered the patient, so that his health and strength may be 
maintained at a normal level. It is readily appreciated that 
these two guiding principles of treatment are diametrically 
opposed to one another in many respects. The one demands a 
restricted diet, and in many instances, undernutrition;, the 
other calls for a lartrer amount of food. The first aims at treat- 



Apkil, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



95 



ing the disease, diabetes mellitus ; the second attempts to con- 
serve tlie nutrition of the patient. The neglect of either factor 
may entail undesirable results. 

During the jjast years, emphasis has been continually placed 
upon the dietary restriction and the prevention of glycosuria. 
Previously, on account of lack of full appreciation of the results 
which could be obtained by a more drastic curtailment of the 
food calories, this idea was not pushed to its logical conclusion 
of controlling the glycosuria of nearly every diabetic patient. 
Through the efforts of F. M. Allen, by systematic and radical 
reduction in the food, this may be easily accomplished in most 
cases.'' The widespread use of these very limited diets has 
brought up the question of how little the individual may eat 
and yet remain physically and mentally fit. It is the object of 
the present paper to furnish at least a partial answer to this 
problem. 

The standard for maintenance for the diabe1;ic may be sought 
in one of two criteria ; first, the caloric requirement, and 
second, the nitrogen equilibrium. The caloric requirement 
may be readily ascertained according to the height-weight for- 
mula of Du Bois and Du Bois.' Food administered in accord- 
ance with this standard ' should satisfy all theoretic demands. 
The nitrogen equilibrium represents the lowest possible diet 
which could be exacted of any patient. Food, under these cir- 
cumstances, results in the conservation of the protein tissues, 
but does not necessarily prevent the loss of fat. This principle 
has been api^lied in the treatment of obesity; it was success- 
fully used in the prolonged dietetic experiments of Chittenden 
on normal people, and is employed here. No living being can 
afford to lose muscle and glandular tissue indefinitely. How 
far the fat store of any individual may be depleted with advan- 
tage is another question. There is much to be said in favor 
of allowing the diabetic to become thin, so that his metabolism 
may be established at a lower level, as has so frequently been 
urged, but it should be distinctly appreciated that this loss of 
weignt sliould occur in the fats and not in the vitally necessary 
proteins. It is with these ideas in mind that the nitrogen 
equilibrium has been chosen as the lowest possible food stand- 
ard by which diabetics may be maintained in a state of physical 
and mental well-being over longer periods. 

Tal)le 1 presents a siimmary of some of the cases studied. 
All of these patients were given diets of the same relative pro- 
portion of fats and proteins. These two food substances were 
maintained equal to each other, gram for gram, as nearly as 
possible. Only such carbohydrates were given as were unavoid- 
ably present in the green vegetables. In this way, these 
patients received diets which made a comparison as to the effect 
on the nitrogen equilibrium possible. From the table it may 
be noted that diabetic patients may be established in nitrogen 
equilibrium by a carljoliydratc-frec diet having a caloric' \aliii' 



•Allen, F. M.: Boston Med. and Surg. Jour., 1915, CLXXII, 241. 

= Du Bois, D., and Du Bois, E. P.: Arch. Int. Med., 1916, XVII. 
863. 

= Gephart, F. C, and Du Bois. E. F.: Arch. Int. Med., 1916, XVII. 
902. 



equal to the standard total caloric requirement. In many 
instances, this may be accomplished at a considerably lower 
level of feeding. The lowest diet which will conserve the 
physical and mental efficiency of the diabetic is that which 
maintains the nitrogen equilibrium. A rough estimate for 
clinical purposes of what constitutes a maintenance ration for 

TABLE 1 

Caloeic Requirkmext Necessary to Produce Nitrogen" Equi- 
librium IX Cases of Diabetes Mellitus, as Cojipared with 
THE Normal Metabolism of Individuals of the Same Age axd 
Sex. a Summary of Some of the Cases Studied 



I. Period I.| 38 
Period 2.) . . 

2 35 

3 1 43 

4 on 

.5 26 



M. Very poor 



Calories per hour per 

square meter of 

body surface 



F. Fair 

M. Poor 

F. Normal 

M. Fair 

J.tM. Normal 

7 41 M. Normal 

S. Period 1. 13 M. Normal 

Period 2.1 1 

9 12 F. Poor 



41.6 
41.6 
31.6 
36.3 
18.2 

ssis 

45.6 
49.7 
37.7 
36.4 



47.2 
47.4 
39.7 
43.7 
27.0 
35.9 
28 2 
49.1 
39.5 
51.7 



Caloric requirements 
necessary to establish 
K equilibrium as com- 
pared with normal 
metabolism 



43.7 
43.7 
40.6 
43.7 
36.0 
43.7 
43.7 
43.7 
54.9 
54.9 



S per cent Iiiglier 
8 per cent higlier 
L'nclianged 
Unchanged 
25 per cent lower 
18 per cent lower 
2S per cent lower 
12 per cent higher 
128 per cent lower 
16 per cent lower 



* Basal metabolism according to F. C. Gcphart and E. F. Du Bois (Arch. Int. Med 
1916, XVII, 902), plus 10 per cent to allow for the specific dynamic action of the diet. 

the diabetic on a carbohydrate-free diet is from 1500 to 2000 
calories. In adjusting the value of the diet, it should be borne 
in mind that women and small individuals generally require 
less food than men and larger individuals. 

Certain other facts were developed in the course of this 
study which are not brought out in the table, but Which may 
be briefly summarized as follows: The factors which deter- 
mine tlie dietary level at which a diabetic maintains a nitrogen 
balance are apparently very numerous and not fully deter- 
mined ; glycosuria at times, and infections, even of very slight 
degree, may necessitate a higher diet to bring about the desired 
result. .A- marked assimilation of nitrogen may occur in dia- 
betics while on a carliohvdrate-freo diet. 



THE EFFECT OF DIET ON BLOOD SUGAR IN DIABETES 

MELLITUS. (.\bstract) 
By Hermax O. Mosexxhal, Sajuel W. Cl.\usex and Alma Hii.lek 
^From the Medical Clinic of The Johns Hopkins Hospital) 
Aside from its physiological interest, it was lioped that this 
investigation would yield information which would enable the 
clinician to interpret blood-sugar values taken at any time of 
the day. The blood sugar was determined at hourly intervals 
in cases of diabetes mellitus. The patients were ordered diets 
which were adjusted to the therapeutic needs of the individual, 



96 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 326 



that is, they were " carbohydrate-free,"' contaiuing no starch 
except that present in green vegetables, or, except in a very 
few instances, limited in starch content so that the glycosuria 
was held in abeyance or at a low level. The results obtained 
under these circumstances, while they do not exhaust the 
subject from the physiological or pathological physiological 
])oint of view, are applicable to the practical interpretation of 
blood sujiars in the treatment of diabetes mellitus. 



TABLE 1 
SUJIMARY OF THE HOURLY DETEBJIINATIOXS OF BLOOU ScGAR IN CASES 

OF Diabetes Mellitus ox a Carbohydrate-Free Diet,'or Oxe 

CONTAl.NIXG a MoDEKATE AmOUXT OF STARCH. If ThERE IS A 

Rise of Blood Sugar ix the Course of the Day', the Maxijiai. 
Value Reached One or Two Hours after Breakfast is 
Usually' not Exceeded to axy- Marked Degree after Lunch 
or Supper. There Frequextly- is a Diminution ix the 
Glycemia in the Afternoon and Evening. 



Blood sugar per cent 





After b 


eaktast 


After lunch 


After 


supper. 


Fasting 












Maximal 


Minimal 


Maximal 


Minimal 
.13 


Maximal 


Minimal 


.IS 


.IS 


.17 


.17 


.17 


.11 


.45 


.4.T 


.4.". 


.4:') 


.4.') 


.4.j 


.4.") 


.23 


.23 


.2:! 


. 23 


. 23 


. 23 


.Ill 


^ .33 


. :!.•! 


.:i:i 




. 32 




.2S 


.18 


.IS 


.IS 


.1!! 


.IS 


.IS 


.IS 


.17 


.17 


.17 


.IS 


.IS 


.IS 


. IS 


.12 


.19 


.Iti , 


.20 


.16 


.Hi 


.14 


.1.5 


.1!) 


.15 i 


.19 


.11 


.17 


.1.1 


.14 


.l(i 


.Hi 


.18 


.1« 


.Hi 


.10 


.13 


.Iti 


.13 


.14 


.08 


.IS 


.1.'. 


.k; 


.2.') 


.23 


. 23 


.22 


2(i 


■7.) 


.14 


.17 


.14 


.17 


.17 


.17 


.15 



Tlie maximal percentage of blood sugar occurring in diabetic 
individuals on a carbohydrate-free diet, or one containing a 
moderate amount of starch, may be obtained one to two hours 
after breakfast. The glycemia may rise somewhat higher after 
lunch or supper, but never to any marked degree. Ou the 
other hand, tlie blood sugar may fall considerably in the after- 
noon and evening hours, leading to crniiiccms iiitorprciations 
if taken only at this time of the day (Table 1 ) . 

Ill diiihetie cases there is a tendency for tlic blood sugar i<> 
remain constant throughout the day wliilc on a iirofciii-rat 
diet, if the fasting blood sugar is high: on the other liand. if 
the fasting blood sugar is low, that is, if it has been reduced liv 
previous dietetic treatment, there is an iiicrea.se in the glycemia 
after carbohydrate-free food, which may become very marked 
(Table 1). This leads to the conclusion that diaitetic 
])atients, by raising their fasting or ba.sal blood sugar ])er- 
centage, tend to adjust their carboliydrate metabolism in such 
a manner that they are able to utilize the food offered them 
to better advantage. It may be desirable, therefore, not to 
attempt to induce the blood sugar to a normal value in all cases 
of diabetes mellitus. 



A RARE TYPE OF BLADDER ULCER: FURTHER NOTES, 
WITH A REPORT OF EIGHTEEN CASES' 

By Guy L. Hixxer, M. D., Baltimore, Md. 

(Abstract from the Journal of the American Medical Association, 
1918, Vol. LXX, 203.) 

The author refers to his original piublicatioii in The Trans- 
actions of the Southern Surgical and Gynecological Associa- 
tion in 1914, in which eight cases were described of a type of 
bladder ulceration hitherto unreported. 

The lesion is a chronic infiltration of all coats of the blad- 
der wall, usually of broad extent in the vertex or free portion 
of the bladder, and presenting one or more minute superficial 
ulcers in the mucosa layer. 

The urine is always macroscopic-ally clear but on carefully 
pipetting and centrifuging, one can find microscopically a few 
leukocytes and a few erythrocytes. Culture of the urine is 
always negative. 

The symptoms are those of an intense and most painful 
cystitis, usually having extended over a period of many years, 
and being iminfluenced or only partially allayed by the usual 
methods of cystitis treatment, 

111 addition to the bladder pain, strangury, and frequency 
of voiding, there are often referred pains to the intestines, and 
especiallj' to the rectum, to the lateral pelves and hips, ami 
down the thighs, and to the vagina and perineal region. 

The etiology of this type of bladder inflammation is still a 
matter for investigation. In one of the 18 cases there was 
a history of a colon bacillus cystitis following an Alexander 
operation 18 years previously. With this exception, none of 
the cases could be traced to a past operation, catheterization, 
childbirth, or gonorrhea, the frequent forerunners of a chronic 
cystitis. The fact that many of the patients refer the begin- 
ning of their symptoms to childhood or early adult life makes 
one tliiiik of the possibility of a focal infection as the etiologi- 
cal faitor. The fact that the lesion is fomid in the vertex 
or free portion of the bladder rather than in the base, when- 
are found the chief blood and lymph connections, is probably 
an argument against the focal infection theory. 

As stated above, cultures from the urine are always sterile. 
In several cases the fresh tissues taken at operation have been 
macerated and used for anat'robic cultures with uniformly nega- 
tive results. Many slides have been prepared with various 
stains in an attempt to demonstrate microorganisms in the tis- 
sues, but with negative results. 

The successful treatment of these cases depends upon a com- 
plete excision of the entire area of infiltration, and this often 
involves the major portion of the bladder. One is surprised 
after repeated careful cystoscopy, which usually reveals an 
ajiiJarently superficial inflammatory condition limited to a 
coin])aratively small ]iortion of the vertex of the bladder, to 
find at operation a widespread edema of the bladder mucosa. 



' Paper read in the Section on Obstetrics, Gynecology, and 
Abdominal Surgery at the sixty-eighth annual session of the 
American Medical Association in New York City. June 7, 1917. 



Apkil, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



97 



subtended by thickening and infiltration of all coats of the 
bladder. 

The excision must include the entire edema area, and the 
histologic study of the removed specimen shows that the 
chronic inflammation of the walls is coextensive with the area 
of edema. This explains the futility of local treatments. 

The past failure of urologists to discover this lesion in spite 
of the patient's intense and persistent bladder symptoms has 
been due chiefly to three factors. First, careless urinary 
analyses have overlooked the few leukocytes and erythrocytes 
present in an otherwise normal urine. Seeing a macroscop- 
ically clear urine and failing to grow a culturehas led to a 
careless and negative microscopic examination, or on finding 



a few leukocytes and erythrocytes these have been dismissed 
as of no significance. Second, the minute and superficial 
character of the ulcer portion of the lesion has caused it to be 
entirely overlooked or its importance to be ignored. Third, 
the usual location of the lesion in the vertex or on the anterior 
wall back of the symphysis is the most difBcult portion of the 
bladder to explore by either the Nitze or Kelly methods of 
cystoscopy. 

The extra-vesical or referred pain ]>heiiomena liave led to 
many errors of diagnosis, 9 of the 18 patients having had 
a total of 16 operations directed toward the relief of their 
symptoms. These operations were largely futile because of a 
failure to make a proper diagnosis. 



PROCEEDINGS OF SOCIETIES 



THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY 
DECEMBER .(, j:)17 
1. Exhibition of a Case of Psoriasis. Dk. Lloyd W. Ketho.n. 

This case is f)resented to the Society because of the remark- 
able shape of the lesions. The patient is a young man, aged 
29, and is engaged in work of a clerical nature. lie has had 
psoriasis for four years. The disease has only once entirely 
disappeared from his body, remaining away for about four 
months. It was during the second attack that the lesions took 
on the unusual contour which they now present. During the 
first attack, they were of the discoid type. 

At the jjresent time (see photograph), the disease is ratlier 
widely disseminated over the entire body. The most striking 
lesion is a band on the left side, about an inch and a half wide, 
extending from beneath the axilla with a serpentine contour 
down to the pubic region. There is a similar band on the right 
side of the body. On the thighs, and back, some of the lesions, 
although much smaller, are also coiled in a snake-like manner. 
Besides this serpentine arrangement, there are a few lesions 
of the discoid, or guttate variety. 

The usual types of psoriasis are the punctate, guttate, discoid, 
Mild irregularly shaped patches of larger size. Occasionally, 
there is an annular form, and sometimes, when the lesions 
coalesce, a gyrate configuration may result. I have, however, 
never seen lesions showing such a clear-cut serpentine contour, 
as the ones in the present case. According to the patient's 
history, these bands were fonncd from the confluence of round 
l)atches, which a])|)eare(l in the lines wliich the present lesions 
have now assumed. 

In answer to Dr. Browji's (|iiestioii as (o tiie trcatnieiiL of 
psoriasis ; there is nothing radically new at the present time, 
that promises to be of special value, f'hrysarobin ointment 
still seems to be our most eflficieiit i-rmedy. It is, however, 
very unpleasant for tlie jiatieiii. to use, heeaiise it stains all the 
clothing, and fro([uen(iy sets up a dermatitis on the norma] 
skin. 

The injection of autogenous serum was ratliiM' entlmsias- 
tically Used for a while, but the work of Dr. Willock in our 



de])ai'tnient gave practically negative results. Interesting 
iiietahiilir studies in psoriasis cases have been lately carried 




on by Sehamberg and his associates in Philadelphia. They 
have shown that there is a nitrogen retention, and have claimed 
good results in treatment by giving a low protein diet. 



98 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 326 



The X-ray is of very great value in cases which have just a 
few very persistent chronic patches of psoriasis. These patclies 
usually respond very quickly to one or more suberythema 
doses. 

2. The Use of Relaxation Incisions in Dealing with Extensive 
Unstable Scars. Db. John Staige Davis. 

Introduction. — Tlie treatment of tightly stretched unstable 
scars, which frequently break down, has long been a source of 
worry to the surgeon and of distress to the patient. 

This type of .scar usually follows extensive deep burns or 
loss of tissue by trauma where the wound has been allowed to 
heal by the slow process of cicatrization, without the aid of 
skin-grafting or of plastic operation. 

The original wounds are always large and usually involve 
the entire circumference of a part, such as the leg or thigh, 
or occasionally the calvarium. In other words, the scar sur- 
rounds and compresses the part. 

Some of the scars are bluish red with fine superficial vessels ; 
others are pale and seem to have little or no blood supply. 
Frequently there are superficial ulcers of various sizes scat- 
tered over the surface. The sears are as unstable as wet 
tissue paper and the slightest injury will start an ulcer that 
will take weeks to heal. 

TJiere is little resistance to trauma or infeetion, and ;iii 
area that is healed, in a very short time and without ;iiiy 
apparent cause, nuiy brciik dnwn riiiirrly: iw niuilipic uK'crs 
may develop. 

A number of these cases have come under my care, and fur 
a long time gave me much trouble. After using many methods 
with little success, it occurred to me to try relaxation in- 
cisions and to graft the defects thus made. 

Technic. — It is preferable that the area be entirely healed 
before the incisions are made, but in some instances where the 
cicatrization of the superficial ulcers has been extremely slug- 
gish I have not waited for complete healing, but have operated 
as soon as the granulations have been brought into a healthy 
condition. Before operation in the unhealed cases, after the 
granulations have become healthy, the part is put up in a 
dressing kept wet with normal salt solution for 24 hours. 
The granulations are then painted with tincture of iodine nnd 
the surrounding scar is cleaned with ether and alcohol. 

Not infrequently the relaxation incisions can be made after 
infiltration with a local anesthetic, such as Schleich's solution, 
or one-half per cent novocain. In other instances a general 
anesthetic is advisable, especially if large immediate Thiersch 
grafts are to used to cover the defect. 

On an arm or leg long incisions should be made, parallel to 
the long axis of the part, down to the deep fascia, or down to 
healthy tissue if the destruction has been deeper than tlie 
fascia. Three relaxation incisions are usually sufficient for a 
limb and result in gaping wounds. 

Remarks. — The immediate spreading of eacli relaxation 
incision varies with the tightness oC the scar. Tn some 



instances it is as much as 2.5 to 3 inches at the center of the 
incision. The spread of the first incision is, of course, the 
widest. 

After the tension has been relieved the appearance of the 
scar tissue between the incisions soon changes, and instead 
(jf retaining the thin, glossy, mottled look, the tissue seems to 
thicken and to acquire greater stability. This improvement 
is much more marked after a few days. 

When the scar is stretched over a broad expanse of bone, 
such as the skull, as many horizontal incisions as may be 
necessary should be made down to the periosteum. The spread 
of relaxation incisions over bone is not so marked as over soft 
parts, and some undercutting may have to be done. In these 
cases the beneficial efl'ect is more marked after a week or two, 
but in the end the result is very satisfactory. 

In some cases of very long standing the tissue exposed by 
relaxation incisions has atrophied from pressure and lack of 
use and has such a poor blood supply that immediate grafting 
is unwise. In these cases it is advisable to wait for several 
days until the wounds are lined with granulation tissue and 
then to apply the grafts. 

In other instances immediate grafting is justified, but this 
point must be determined at the time of the operation. 

It is extraordinary to note the rapidity of healing of the 
superficial ulcers after the relaxation incisions are made. 

I have used only snnill deep grafts and Thierscli grafts on 
the defecti^ caused by the relaxation incisions. These grafts 
h;i\(' lieen .>«) Car entirely satisfactory, however, that there 
seems to be no reason why grafts of whole-thickness skin should 
not be used in cn^cs where this type of graft may be nece^ssary. 

There has been no recurrence of superficial ulceration in 
any case where the tension has been completely relieved by 
the method described above. 

Conclusions. — By the use of relaxation incisions with im- 
mediate or subsequent skin grafting of the defects, large 
unstable scars can be firmly healed in a comparatively short 
time, and j)atients who have been incapacitated for many 
months can resume their usual occupations. 

I have used this method on a number of cases, with uniform 
suci'css, and feel that it is a rational procedure and well worth 
trying. 

3. Observations on Bird Malaria and the Pathogenesis of Relapse 
in Human Malaria. I.iErr.-Cot.oNKi, Eccnnk R. Whitmori:. 
.•\rniy Medical School, Wasliington, 1). C. 

Published in the ^larcii numlier of the Bulletin. 
DECEMBEii n. inn 

1. The Preparation of the U. S. Army Triple Typhoid Vaccine 

(Illustrated with Moving Pictures). Ma.iou C. G. Snow, .Army 
iModical Srliool. AViisiiington, 1>. (". 

To lie published in a liiter nuniher ol' the IlrLLK'i'IN. 

2. Recent Work on the Differentiation of the Paratyphoid Group 

in Relation to Disease in Man. Dk. CiiAKr.K.s KBUMWiEDt, 
DepartniPnt of Health, New York City. 



April, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



99 



DISCUSSION 

Dr. W. W. Foed. — Of course it is very gratifyiug to me to 
find that a distinction between the various types of paratyphoid 
bacilli made out so many years ago has been confirmed by 
Dr. Krimiwiede in a manner which is more comprehensive than 
that shown in the original suggestion. 

There are many extremely interesting features about this 
group. In the original work upon the paratyphoid organisms, 
I was impressed by the fact that practically all of the para- 
typhoid cultures rendered milk alkaline if you gave them 
suiScient time to act. That is to say, the old distinction 
between paratyphoid A and B, based upon the production 



of permanent acidity in milk in the one group, and the loss 
of acidity and production of alkalinity in the other, was not 
a valid distinction. The two groups could be differentiated, 
however, by the use of the higher polysaccharids, such as 
arabinose and xylose. One reason for the reported stability of 
Bacillus enteritidis of Gartner is that so few cultures of this 
organism are available for study. The majority of those 
found in America for instance, are derived from a culture sent 
to The Johns Hopkins many years ago by Dr. Durham, of 
Cambridge, England. It is interesting to note how Dr. Krum- 
wiede's studies have enabled bacteriologists to trace the origin 
of many of these strains back to their original animal host. 



BOOKS RECEIVED 



obstetrics for Nurses. By Charles B. Reed, M. D. 134 illustrations. 
1917. 12°. 374 pages. C. V. Mosby Company, St. Louis. 

A Text-Book of Anatomy for Nurses. By William Gay Christian, 
M. D. With 34 original illustrations, 5 of which are in colors. 
1917. 12°. 222 pages. C. V. Mosby Company, St. Louis. 

Fiske Fund Prize Essay No. LTII. The Role of the Teeth and Ton- 
sils in the Causation of Arthritis. By Dr. Joseph F. Hawkins. 
1917. 8°. 29 pages. Snow & Farnham Co., Providence, R. I. 

The Child in Health and Illness. By Carl G. Leo-Wolf, M. D. 
Illustrated. 1917. 8°. 297 pages. George H. Doran Company, 
New York. 

Royal Academy of Medicine in Ireland. Transactions. Volume 
XXXV. Edited by J. Alfred Scott, M. A., M. D., F. R. C. S. I. 
1917. 8°. 292 pages. John Falconer, Dublin. 

The Institutional Care of the Insane in the United States and 
Canada. By Henry M. Kurd, William F. Drewry, Richard 
Dewey, Charles W. Pilgrim, G. Alder Blumer and T. J. W. 
Burgess. Edited by Henry M. Hurd, M. D., LL. D. Volumes 
111 and IV. 1916-1917. 8°. 880 pages; 652 pages. The Johns 
Hopkins Press, Baltijnore, Md. 

Clinical Cardiology. By Selian Neuhof, B. S., M. D. 1917. 8°. 
302 pages. The Macmillan Company, New York. 

American Ophthalmological Society. Transactions. Volume XV. 
1917. 8°. 332 pages. American Ophthalmological Society, 
Philadelphia. 

The Prescription, Therapeutically, Pharmaceutically, Grammati- 
cally and, Historically Considered. By Otto A. Wall, Ph. G., 
M. D. Fourth and revised edition. 1917. 8°. 274 pages. 
C. V. Mosby Company, St. Louis. 

Diseases of the Skin. By Richard L. Sutton, M. D. With 833 
illustrations and 8 colored plates. Second edition, revised and 
enlarged. 1917. 8°. 1021 pages, C. V. Mosby Company, 
St. Louis. 

Metropolitan Asylums Board. Annual Report for the year 1916. 
(19th year of issue.) 1917. 8°. 55 pages. Sylvan Grove. 
London. 

Human Physiology. By Professor Luigi Luciani. Translated by 
Frances A. Welby, with a preface by J. N. Langley, F. R. S. 
In five volumes. Vol. IV. Edited by Gordon M. Holmes, M. D. 
The 8e7ise Organs. 1917. 8°. 519 pages. Macmillan & Co., 
1917. 



The School Nurse. A Survey of the Duties and Responsibilities 
of the Nurse in the Maintenance of Health and Physical Per- 
fection and the Prevention of Disease among School Children. 
By Lina Rogers Struthers, R. N. With 24 illustrations. 1917. 
12°. 293 pages. G. P. Putnam's Sons, New York and London. 

International Clinics. A Quarterly of Illustrated Clinical Lectures 
and Especially Prepared Original Articles. By leading mem- 
bers of the medical profession throughout the world. Edited 
by H. R. M. Landis, M. D. Volume III, Twenty-seventh series. 
1917. 8°. 306 pages. J. B. Lippincott, Philadelphia and 
London. 

A Reference Handbook of the Medical Sciences. Embracing the 
Entire Range of Scientific and Practical Medicine and Allied 
Science. By various writers. First and second editions edited 
by Albert H. Buck, M. D. Third edition completely revised 
and rewritten. Edited by Thomas Lathrop Stedman, A. M., 
M. D. Complete in eight volumes. Volume 8. Illustrated by 
numerous chromolithographs and 337 half tone and wood 
engravings. 1917. 4°. 782 pages. William Wood & Co., 
New York. 

The Principles of Acidosis and Clinical Methods for its Study. By 
Andrew 'Watson Sellards. 1917. 8°. 117 pages. Harvard 
University Press. Cambridge. 

St. Luke's Hospital. Medical and Surgical Reports. Volume IV. 
1917. 8°. 404 pages. The Press Publishing Co., East Strouds- 
burg. Pa. 

A Treatise on Regional Surgery. By various authors. Edited by 
John Fairbairn Binnie, A. M., C. M., F. A. C. S. Volume II. 
With 213 illustrations. 1917. 8°. 656 pages. P. Blakiston's 
Son & Co., Philadelphia. 

Radium Therapy in Cancer at the .Memorial Hospital, Xeio York. 
(First Report: 1915-1916.) By Henry H. Janeway, M. D. 
With the discussion of treatment of cancer of the bladder and 
prostate, by Benjamin S. Barringer, M. D., and an introduction 
upon the physics of radium, by Gioacchino Failla, R. E., A. M. 
1917. 8°. 242 pages. Paul B. Hoeber, New York. 

Recollections of a Neio York Surgeon. By Arpad G. Gerster, M. D. 
1917. 8°. 347 pages. Paul B. Hoeber, New York. 

White and Martin's Genito-Urinary Surgery and Venereal Diseases. 
By Edward Martin, A. M., M.TJ., F. A. C. S. Benjamin A. 
Thomas, A. M., M. D., P. A. C. S., and Stirling W. Moorhead, 
M. D., F. A. C. S. Illustrated with 422 engravings and 21 
colored plates. Tenth edition. 1917. S°. 929 pages. J. B. 
Lippincott Company, Philadelphia and London. 



100 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 336 



Technique of Operations on the Bones, Joints, Muscles and Ten- 
dons. By Robert Soutter, A. B., M. D. (Harvard.) 1917. 
8°. 350 pages. Macmlllan Company, New York. 

Publications of the Houth African Institute for Medical Research. 
Edited by W. Watkins-Pitchford, .M. D. (Lend.) No. IX. 
(1) Lysed Bacterial Serum. (2) Further Observations on 
Piantication. (3) A Note on Phagocytosis in the Abse7ue of 
Serum. By A. R. Frlel, M. D., F. R. C. S. I., and F. S. Lister. 
M. R. C. S., L. R. C. P. 1917. 4°. 14 pages. Printed by \V. E. 
Hortor & Co., iM., Johannesburg. 

Monographs of the Rockefeller Institute for Medical Research. 
JVo. 7. Acute Isobar Pneumonia, Prevention and Serum Treat- 
ment. By Oswald T. Avery, M. D.; H. T. Chickering, M. D.; 
Rufus Cole, M. D., and A. R. Dochez, M. D. 1917. 4°. 110 
pages. The Rockefeller Institute for Medical Research, New 
York. 

A Handbook on Antiseptics. By Henry Drysdale Dakin, D. Sc, 
F. L. C, F. R. S., and Edward Kellogg Dunham, M. D. 1917. 
24°. 129 pages. Macmillan Company, New York. 

Elements of Hygiene and Public Health. A Text-Book for Students 
and Practitioners of Medicine. By Charles Porter, M. D., 
M. R. C. P. (Edin.) With 98 illustrations. 1917. 12°. 411 
pages. Henry Frowde; Hodder & Stoughton, London. 

Elements of Field Hygiene and Sanitation.. By Joseph H. Ford, 
B. S., A. M., M. D. Approved for publication by the Surgeon- 
General U. S. Army. 1917. 248 pages. P. Blakiston's Son & 
Co., Philadelphia. 

Diseases of Women. By Harry Sturgeon Crossen, M. D., F. A. C. S. 
Fourth edition, revised and enlarged. With 800 engravings. 
1917. 8='. 1160 pages. C. V. Mosby Company, St. Louis. 

The Treatment of Infected Wounds. By A. Carrel and G. Uehelly. 
Translation by Herbert Child, Captain R. A. M. C. (Ty.) With 
introduction by Sir Anthony A. Bowlby, K. C. M. G., K. C. V. O., 
F. R. C. S. 1917. 12°. 238 pages. Paul B. Hoober, New York. 

Medical Diagnosis. For the Student and Practitioner. By Charles 
Lyman Greene, M. D. With 14 colored plates and 548 other 
illustrations. 1917. 8°. 1302 pages. P. Blakiston's Son & Co., 
Philadelphia. 

The Destiny of the American Surgical Association. My J. Iilwing 
Mears, M. D., LL. D. Reprinted from the Transactions of the 
Association, Vol. XXXV, 1917. 1917. 8°. 12 pages. Wm. J. 
Dornan, Philadelphia. 



Royal College of Surgeons of England. Calendar. 1917. 8°. 407 
pages. Taylor & Francis, London. 

Impotence and Sterility. With Aberrations of the Sexual Function 
and Sex-Gland Implantation. By G. Frank Lydston, M. D., 
D. C. L. 1917. 8°. 333 pages. The Riverton Press, Chicago. 

An Introduction to the History of Medicine. With Medical Chro- 
nology, Suggestions for Study and Bibliographic Data. By 
Fielding H. Garrison. Second edition, revised and enlarged. 
1917. 8°. 905 pages. \V. B. Saunders Company, Philadelphia 
and London. 

A Manual of Anatomy. By Henry Erdmann Radast-h, M. Sc. 
M. D. With 329 illustrations. 1917. 8°. 489 pages. W. B. 
Saunders Company, Philadelphia and London. 

Studies from the Rockefeller Institute for Medical Research. 
Reprints. Volume XXVII. 1917. 8°. 559 pages. The Rocke- 
feller Institute for Medical Research, New York. 

A Text-Book of War Niirsing. By Violetta Thurstan. 1917. 12°. 
227 pages. G. P. Putnam's Sons, London and New York. 

A Practical Dietary Computer. By Amy Elizabeth Pope. 1917. 
12°. 156 pages. G. P. Putnam's Sons, New York and London. 

The Principles of Mental Hygiene. By William A. White, M. D. 
With an introduction by Smith Ely Jellife, M. D., Ph. D. 1917. 
12°. 323 pages. The Macmillan Company, New York. 



Talks on Obstetrics. By Rae Thornton LaVake. 1917. 
pages. C. V. Mosby Company, St. Louis. 



157 



Intermediate Text-Hook of Physiological Chemistri/ with Ex- 
periments. By C. J. V. Pettibone, Ph. D. 1917. 80. 328 pages. 
C. V. Mosby Company, St. Louis. 



Physical Diagnosis. By W. D. Rose, M. D. 294 illustrations 
8°. 499 pages. C. V. Mosby Company, St. Louis. 



1917 



Surgery and Diseases of the Mouth and Jaws. A Practical Treatise 
on the Surgery and Diseases of the Mouth and Allied Struc- 
tures. By Vilray Papin Blair, A. M., M. D., F. A. C. S. Third 
edition, revised so as to incorporate the latest war data con- 
cerning gunshot injuries of the face and Jaws. With 460 
illustrations. 1917. S' . 733 pages. C. V. Mosby Company, 
St. Louis. 

The Medical Association of the State of Alabama. Transactions. 
1917. 8°. 632 pages. The Brown Printing Company, Mont- 
gomery, Ala. 



NEW PUBLICATIONS. 



The following six monographs : 

Free Thrombi and Ball-Thrombi in the Heart. By J. H. 
Hewitt, M.D. 82 pages. Price, $1.00. 

Benzol as a Leucotoxin. By Laurence Selling, M. D. 60 
pages. Price, $1.00. 

Primary Carcinoma of the Liver. By M. C. Winternitz, 
M. D. 42 pages. Price, 75 cents. 



The Statistical E.\perience Data of The Johns Hopkins Hos- 
pital, Baltimore, Md., 1892-1911. By Frederick L. 
Hoffman, LL.D., F.S.S. 161 pages. Price, $2.00. 

The Origin and Development of the Lymphatic System. By 
Florence R. Sarin. 94 pages. Price, $2.00. 

The Nuclei Tuberis Laterales and the So-called Ganglion 
Opticum Basale. By Edward F. Malone, M. D. 
Price, $1.50. 



are now on sale by The Johns Hopkins Press, Baltimore. Other monographs will appear from time to time. 



The Johns Hopkins Hospital Bulletins are issued montlily. Thev are printed Jj/ the LORD BALTIMORE PRESS, Baltimore. Suiscriptions, $3.00 
a year (.foreign postage, 50 cents), may be addressed to the publishers. 'IBB JOHNS HOPKINS PRESS, BALTIMORE; single copies tcill be sent hy 
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BULLETIN 



OF 



THE JOHNS HOPKINS HOSPITAL 



Entered as Second-Class Matter at the Baltimcire. Maryland. Postottire 



Vol. XXIX^No. 327] 



BALTIMORE, MAY, 1918 



[Price, 50 Cents 



Tlie Results of Treatment in Pernicious Anemia. 
Bv Arthur Bloomfield. M. D. . . . 



Tobacco Smoke and Pulmonary Tuberculosis. 
By Allen K. Krause 



CONTENTS 

PAGE PAGE 

Memorial Services in Honor of Franklin I'aine Mall. Professor 
. 101 I of Anatomy, Johns Hopkins University. lSJ):i to 1917. 

(Illustrated.) 109 

I In Memoriara 124 

. 106 Notes on New Books 125 



THE RESULTS OF TREATMENT IN PERNICIOUS ANEMIA 

By Artiui; BijiO-MFIELD. ]\I. D. 
(From the Medical Clinic of The Johns Hopkins Hospital) 



The treatment of j^ernicious anemia, generally employed 
until a few years ago, consisted of a regimen in which rest, 
special diet, and the administration of arsenic were the princi- 
pal features. Recently more radical measures have come into 
prominence, namely, transfusion of blood, splenectomy, and 
operations for the elimination of " foci of infection."' The 
reports on these newer methods have dealt so far mainly with 
general considerations and immediate results: 

Ottenberg and Libman ' state that transfusion leads to re- 
mission in about one-half of the cases. Archibald ^ found that 
of 26 patients who received transfusions G9 per cent derived 
marked immediate benefit. Larrabee ^ from a small experience 
(six cases), and Barker and Sprunt* feel that if the anemia is 
severe and progressive and resjx)nds poorly to other methods 
transfusion .should be tried, ileleney and his associates," with- 
out making detailed statements, conclude that transfusion is 
of real value in pernicious anemia, spontaneous remissions 
having been hastened in many cases by the procedure. Witli 
regard to splenectomy Lee, Vincent, and Eobertson ° found in 
a series of five cases that the immediate result was prompt post- 
operative recovery and a definite remission of the disease. 
Krumbhaar,' in a review of the late results of splenectomy in 
153 cases, noted a post-operative mortality of about 20 per cent 
and also that the improvement was transient in most of the 
patients. Minot and Lee ' emphasize the importance of care- 
ful selection of cases. Their report includes a thorough study 
of immediate and late results of transfusion and splenectomy 
in a somewhat larger series. They find that these measures, 
wlicn properly employed, offer more than other methods of 
treatment alone, although they may fail in individual cases. 



A recent report by Giilin ' states that splenectomy does not 
cure pernicious anemia but that there is considerable im- 
provement in more than half of the cases, especially when the 
procedure is combined with transfusion. William Hunter 
first emphasized the relation of '' oral sepsis " to severe 
anemias, and recently Barker and Sprunt ' have laid stress on 
the importance of eliminating '• foci of infection " in the treat- 
ment of pernicious anemia. 

Inasmuch as these procedures are elaborate, and at times not 
without immediate ill effects, it seems important to have more 
information as to their value in prolonging life or inducing 
remissions. In this report a series of 57 cases has been analyzed 
in detail with particular reference to the comparative value 
of the various methods of treatment. All the patients were 
studied in the Jledical Clinic of The Johns Hopkins Hospital 
and were selected serially from the records of the past five 
years. In every instance the history, physical findings, and 
the blood picture were typical of tlie so-called idiopathic type 
of pernicious anemia. 

Determination of the value of therapy in this disea.se is 
notably difficult owing to certain features belonging to the 
natural course of the malady. The following possible criteria 
suggest themselves : 

1. The Effect of riraliiwnt on the Total Ditnition of the 
Disease. — This should be the most useful guide. It nuist be 
remembered, however, that the actual on.<et cannot be deter- 
mined, and in only four-fifths of this series was there a clear 
history as to the beginning of symptoms. Furthermore, some 
of the cases run a rapidly progressive course, whereas others 
show repeated remissions. As a rule, the patient is under 



103 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 32^ 



close observation only during the relapses, and the care which 
he takes of himself at other times may influence the course 
of the disease. Thus the reappearance of symptoms has been 
noted not infrequently after exposure, shock, or over-exertion. 
Finally, the advantage of studying large series of hospital eases 
is to some extent offset by the difficulty of tracing many of 
these patients. 

2. The Readiness u-ith wliich Remission is Induced. — Tlii-^ 
furnishes a doubtful standard of treatment, since spontanc<iu~ 
remissions may occur at any time even when the blood count 
has been very low, or after the condition has been stationiuy 
under observation for several weeks or even months. Further- 
more, remissions usually occur more readily in the earlier 
stages of the disease than later; in fact in every case there 
eventually comes a period when all measures are unavailing 
and the downward course is unarrested. This is illustrated l>y 
the cases of several patients in this series who returned to the 
hospital at intervals and finally became totally refractory to 
the measures that seemed before to produce striking results. 

3. The Length of the Remission. — This is often difficult to 
determine. It may vary spontaneously, and depends to some 
extent on the conduct of the patient after leaving the immediate 
care of the physician. 

I. Thf Effect of a Piirlicuhr Form of Therapy on Special 
Sijiiiploiiis is difficult to estimate. — Fever, gastro-intestinal 
disturbances, and the symptoms referable to the anemia itself 
tend to clear up as the remission sets in and the blood im- 
proves. The spinal cord disturbances on the other hand are 
notably but little affected by any therapy, and may even 
progress at a time when the condition seems to be improving 
in other ways. Gain in weight does not always run parallel 
with improvement in the blood count and general condition. 
Tiie degree of the remission, witli reference to the gain in 
blood, may furnish some standai'd nl" tlie ellV'rt of llierapy. 

5. The death rate in ilie hospital ollVrs a means of cnm- 
paring the value of therapeutic measures, but often tiie jiatient 
is in a hite stage of the disease refractory to any treatment. 

(!. 'J'lie Cliaracter of ttie Blood Picture. — Minot and Lee" 
recently report morphological blood studies in pernicious 
anemia which may turn out to be of aid in prognosis and in 
estimating therapeutic effect, but since gain or loss of hhiod 
elements depends on the balance of blood destruction and blood 
formation, patients showing the most active signs of regeiiei-a- 
tion may be doing badly, whereas others may gain rapidly 
without evidence in the i)eriplieral blood of marked marrow 
stimulation. 

Very little information is at hand about the immediate effect 
of transfusion or splenectomy on the blood picture. Lee, Minot 
and ^■ineent'° find immediate stimulation of the bone marrow 
following splenectomy, and JMeleney ° has noted a Icucoeytosis 
shortly after transfusion. 

It is clear that no single standard of tlierapeutic effect is 
reliable. In this report, therefore, the eases have been analvzed 
from these various points of view. 



Kesults of General Treatment 

Twenty-eight cases were treated by the older methods con- 
sisting essentially of rest in bed, diet, hydrochloric acid, anil 
arsenic. The results of such therapy are well known and these 
patients are included mainly as controls to compare with those 
who had transfusion or splenectomy, or in whom foci of 
infection were eliminated. A few points may, however, be 
emphasized. Absolute rest in bed over considerable periods 
of time is certainly the most important feature of this regimen. 
Arsenic and hydrochloric acid are apparently useless, unless 
the patient is kept quiet at the same time, and cessation of 
improvement or relapse has occurred not uncommonly as soon 
as active life was resumed, despite continued drug therapy. 
Furthermore, it often appears on going back into the history 
of the period of the disease before the patient was under medi- 
cal care that the " weakness and shortness of breath " were 
relieved by a few weeks of rest in bed. The value of arsenic 
is based entirely on general impressions. It was used in every 
instance in this series either in the form of Fowler's solution, 
sodium cacodylate, or salvarsan. Analysis of the cases, how- 
ever, yields no data of value as to its efficacy. Achlorhydria 
gastrica was uniformly present and hydrochloric acid was 
given usually both before and after meals. In a few instances 
gastro-intestinal disturbances, especially diarrluxja, seemed to 
be relieved, but in most of the patients these symptoms disa])- 
peared quite rapidly with the progress of the remission appar- 
ently regardless of any symptomatic therapy. In about one- 
half of the cases there were accurate statements as to loss of 
weight. This usually amounted to from 10 to 50 pounds from 
the onset of symptoms to the time of admission to the hospital. 
Unless special features of the case made feeding impossible, 
a liberal diet was allowed. No special dietary regimen or 
restriction of any food element was attempted. No relation 
between gain in weight and improvement in the blood or gen- 
eral condition is apparent in this .series. Of 33 cases in which 
there was clinical improvement, and the weight on admission 
and discharge was recorded, 22 gained and 11 lost. The 
examples in Table I illustrate that gain in blood does not 

TABLE I 



Patient 


Blooil count on 
ndmission 


Blooil count on 
dischart^e 


Diiys in 
hos- 
pital 


Weight on 
admission 
in pounds 


tt'eight on 
discharge 
in pounds 


Loss in 
pound? 


Hu . . . 

H 

B 

P 

G 

S 


% 
2,400,n00 50 
l.IiOO.OdO 20 
1,100.00(1 27 
l.l:!0.000 20 
1,400.000 43 
800.000 22 


% 
3,300,000 76 
3,400,000 00 
4,000.000 02 
3,400.000 00 
3,000,000 GO 
2,200,000 47 


78 
40 
51 
48 
35 
85 


151 
133 
130 
174 
91 
93 


135 
127 
118 
164 
81 
91 


16 
6 
12 
10 
10 
2 



necessarily go hand in hand with gain in weight. After a 
remission is established and digestive disturbances have cleared 
np. rapid gain in weight usually occurs. 

Tii.wsFrsioN 
Twenty-six jiatients received transfusions of blood varying 
in number from 1 to 17. The largest amount of blood given to 
one patient was 8700 cc, the smallest amount was 300 cc. The 



May, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



103 



single transfusions varied in amount from 300 to 900 cc. Tlie 
citrate method and the Lindemau syringe method were used 
most often ; in a few cases indirect transfusions of defibrinated 
blood were given, and in one case direct transfusion was used 
as a preliminary to splenectomy. The technique employed has 
been described recently by JlcC'lure and Dunn," and by Syden- 
stricker, ilason and L'ivers " from this clinic, and will not be 
repeated. 

The therapeutic effect of transfusion in pernicious anemia 
may be discussed under several heads. 

1. The Value of Transfusion as an Emergency Measure. — 
Quite apart from any ultimate effect the question arises 
whether transfusion may tide over a patient during an un- 
usually severe relapse, or may check further fall of the blood 
count where this is very low. To illuminate this point the 
following mortality statistics are presented. Three hundred 
and sixty-three patients with pernicious anemia have been 
treated in The Johns Hopkins Hospital, of whom 58, or Ki 
per cent, died in the wards. Of the 31 who received trans- 
fusion 6, or 19 per cent, died, whereas of the 333 who did not 
receive transfusion 52, or 15.5 per cent, died. Of the 57 cases 
studied in this report, 2(j were given transfusions with (i 
deaths in the hospital — 23 per cent. Of the 32 cases not trans- 
fused and receiving only general therapy, 5, or 33.7 per cent, 
died. Some of the patients were admitted to the hospital 
several times. The patients who were given transfusions had 
37 admissions with 6 deaths, or 16.8 per cent; those not trans- 
fused had 38 admissions with 5 deaths, or 17.8 per cent. 
The cases have been divided further into tho.se entering with 
counts of less than 1,000,000 red cells, and those with counts 
of over 1,000,000 red cells. Patients not receiving transfusion 
were admitted 10 times with counts of less than 1,000,00ii. 
and 18 times with counts of over 1,000,000. Two of the 
former — 30 per cent — died; 3 of the latter, or 17 per cent. 
Of the 37 receiving transfusions 9 entered with counts of 
under 1,000,000 of whom 3, or 33.3 per cent, died ; of the 2S 
with counts over 1,000,000, 3, or 33.3 per cent, died; of the 2S 
with counts over 1,000,000, 3, or 10.7 per cent, died. 

These figures, therefore (Table II), furnish no evidence 
that transfusion was of value as an emergency measure, or 
that the immediate mortality was decreased liy the procedure. 
TABLE II 



Cases receiving 


transfusion 




Cases 
t 


not receiving 
ansfusion 




Num- 
ber 


Deaths 


Num- 
ber 


Dtaths 




Num- 
ber 


Per 
cent 


Num- 
ber 


Per 

cent 




26 
37 

n 

28 


6 
6 

3 

3 


23.0 
16.2 

3:i.3 

10.7 


22 

28 

10 
18 


2 
3 


22.7 




17.8 


Cases with counts under 
1,000,000 


20 


Cases with counts over 
1 000,000 


17 









3. The Immediate Effect of Transfusion. — Following the 
injection of 500 cc. or more of blood there was usually an 
immediate increase in the blood count and hemoglobin. Rises 



of as much as 1,000,000 cells and 15 per cent of hemoglobin 
were frequently noted. In most cases there was a subsequent 
fall. Counts were not made often enough to distinguish the 
purely mechanical result of transfusion from later reactive 
effects. This question is now being studied in detail. Subjec- 
tive improvement was often striking, the patient saying he 
felt better while the blood was being injected. Quite possibly 
this was in some cases a psychic effect. 

3. The Relation of the Onset and Degree of Remission to 
Transfusion. — The cases were studied to find out if remission 
occurred sooner and more often in patients receiving trans- 
fusion than in others. For the purpo.se of this discussion a 
remission is regarded as including marked general and symp- 
tomatic improvement with a gain of at least 1,000,000 red 
cells or 20 per cent of hemoglobin. Among the patients who 
were not transfused remission set in in the hospital 8 times 
in 38 admission!?, a percentage of 28.5; in the patients given 
transfusion there were 19 remissions in 37 admissions, or 51 
per cent. The number of days in the hospital until the highest 
blood count was reached averaged 43 in the untransfused 
patients, and 43 in those receiving blood. The maximal count 
was reached on an average of 34 days after the first transfusion. 

The degree of the remission as measured by gain in blood 
was also studied in the two groups. Counts of 4,000,000 or 
over were reached in 4 cases of the group receiving blood, 
counts of 3,000,000 to 4,000,000 in 9, and counts of 3,000,000 
to 3,000,000 in the remaining 6. Counts of 4,000,000 or over 
were reached only once in the patients who were not transfused, 
counts of 3,000,000 to 4,000,000, only twice, the remaining 
5 patients reaching counts of from 3,000,000 to 3,000,000. 
(iains of over 3,000,000 cells were made in 4 patients receiving 
transfusion, gains of 3,000,000 to 3,000,000 in C, and gains of 
1,000,000 to 3,000,000 in 9. The largest gain in the patients 
who were not transfused was 3,000,000 in one instance, another 
gained 3,000,000 cells, 4 gained from 1,000,000 to 3,000,000 
cells, and 3 gained less than 1,000,000 cells and but 32 per 
cent and 30 per cent of hemoglobin respectively. These facts 
are summarized in Table III. 



Patients'receiving transfusion 


Patients not receiving transfusion 




Remissions 


Number of 
admissions 


Remissions 


Number of 
admissions 


Num- 
ber 


Per 

cent 


Days 
43 


Num- 
ber 


Per 
cent 


Day. 


37 


19 


51 


28 


8 


28.5 


43 


Reaching counts of 


Num- 
ber 


Per 
cent 


Reaching counts of 


Num- 
ber 


Per 

cent 


4,000,000 or over 

3.000,000 to 4,000,000 
2,000,000 to 3,000,000 


4 
!) 
G 


21 
47 
32 


4,000,000 or over . . . 
3,0011.000 to 4.000,000 
2,000,000 to 3,000,000 


1 
2 


12.5 
25.0 
62.5 


Gains of 


Num- 
ber 


Per 
cent 


Num- 
Gainsof ber 


Per 
cent 


3,000,000 or over.... 
2,000,000 to 3,000,000 
1 ,000,000 to 2,000,000 


4 
6 
U 


21 
32 

47 


3,000,000 or over . . . 
2.000,000 to 3.000,000 
1,000.000 to 2,000,000 
or 207o Hb. 


1 

1 
6 


12.5 
12.5 
75.0 



104 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 32; 



The relation of gain in blood to the amount of blood given 
i sliown in Table IV. 



Patient 

and 

number of 

admiBSion 



Number of 
transfu- 
sions 



B. 1 

P. 1 

Pr. 1.... 

P. .T 

H. 1 

B. -J 

Bu. 1... 
Bu.2.... 

S 

E 

M. 1 

A.l 

Bu. 3.... 
Pr. 2.... 

Mur 

S.l 

S£. 2 

O 

H. 

W 

Bre 

M 

Bi 

C 

Wad 

Be 

H. 2 

B. 3 

Horn. .. . 

P. 4 

Ha 

Mu 



Amount of 
blood given 



4400 

3120 

2980 

2S50 

2770 

2500 

2300 

2220 

1650 

1500 

1.500 

1450 

1400 

1325 

1300 

1160 

1150 

920 

800 

7.50 

650 

630 

600 

550 

375 

250 

3500 

1600 

1000 

420 

300 

300 



Gain 
in blood 
(B. B. C.) 



3,000,000 

3,500,000 

2,200,000 

2.300,000 

1,400,000 

2,300,000 

1,, 500, 000 

2.100,000 

1,400,000 

3,000,000 

2,200,000 

1,000.000 

1,100,000 

000,000 

600,000 

1,000,000 

400,000 

500,000 

2,100,000 

300,000 

100.000 

400.000 

3,300,000 

1,800.000 

1,000,000 

600,000 

Died, second. 

Died, coma. 

Died. coma. 

Died, coma. 

Died, coma. 

Died, edema 



Days from 

first 
transfusion 



38 

37 

34 

43 

36 

13 

34 

27 

83 

35 

31 

52 

31 

93 
132 

35 

35 

60 

40 

17 

45 

23 

90 

42 

56 

36 
lues. 



Duration of 
symptoms 
on admis- 



33 

58 
33 

3 

1 

4 
89 
35 
37 
29 
pneumonia. 



of lungs. 



10 mos. 

12 " 

12 '• 

18 " 

12 " 

12 " 

18 " 

12 " 



24 " 
24 " 
3 yrs. ? 

18 mos. 
24 " 



From this table it appears that the patients receiving most 
blood in general made the greatest gains. Thus, of the ID 
gaining 2,000,000 or more cells, 8 received 3 or more trans- 
fusions with a total of l.'iOO cc. or more of blood. None of tho 
.") receiving only one transfusion of less than 1000 cc. gained 
over 1,000,000 cells. Of the 19 cases regarded as having a 
remission all but one received more than one transfusion and 
all but 5 received 1400 cc. or more of blood. 

The success of transfusion seems to depend also on the 
stage of the disease. Where the previous duration of .symptoms 
could be clearly determined in the patients showing a remission 
it was found to be 13 months or less in 10 instances, 18 months 
in 2, and 24 months in 1 case. The importance of the stage 
of tlie disea.se is further illustrated by transfusion results in 
the same patients on n'])eated admissions to the hospital 
(Tahle V). 

In summary, then, it .seems that in patients wbo are not in a 
stage of the disease refractory to any form of treatment, re- 
mission has come on more often when transfusion has been 
performed. Furthermore, the amount of blood gained runs 
rougbly parallel to the number of transfusions and the total 
amount of blood given. It seems rational, therefore, if trans- 
fusion is done at all, to be prepared to inject blood repeatedly 
if the patient shows a tendency to respond. Single transfu- 
sions in cases refractory to other therapy leil to no ini]Ho\em('nt 
in this series. 



4. The Length of the Eemixi-ion. — It was possible to deter- 
mine accurately the length of the remission following trans- 



Patient 

and 

number of 

admission 


Number of 


.\mount of 


Gain nav* from 

in blood rnV,,; 'I,?!D 
(R.B. C.) »omi>,sion 


'Duration of 
Davs from i svmptoms 


transfu- 
sions 


blood given 
c. c. 


first on ad mis- 
transfusion sion 

(approsim.) 


B. 1.... 


5 


4400 


3.000,000 3S 


23 10 mos. 


*B. 2 


3 


2500 


2..SOO,000 13 


9 12 " 


B. 3.... 


3 


1600 severe reactions to homologous 18 " 








blood; death. 




*P. 1.... 


6 


3150 


3,500,000 37 


29 12 •' 


P. 2.... 


5 


2300 


800.000 49 
(34% Hb.) 


47 , 14 " 


P. 3.... 


6 


2850 


2,300,000 43 


38 


18 ■• 


P. 4.... 


3 


420 severe reactions to homologous 


24 " 








blood; death. 






Bu. 1... 


5 


2300 


1,500,0001 34 


24 


12 '• 


Bu. 2. . . 


5 


2200 


2,100.0001 27 


23 


18 " 


Bu. 3... 


4 


1400 


1,100,000 31 


25 


24 •' 


M. 1.... 


3 


1500 


2,200,000 31 


29 


12 " 


M. 2.... 


3 


1150 


400.000 35 


33 


18 " 


Pr. 1.... 





2980 


2,200,000 34 


25 


12 " 


Pr. 2.... 


3 


1325 


900,000 93 


91 


24 " 



* Splenectomy. 

fusion in 13 instances. The return of symptoms with a fall 
in the blood count was regarded as indicating the onset of 
relapse. These data are summarized in Table VI. 

TABLE VI 



Patient 

and 

number of 


.\mou t of 
blood given 


Duration of 

symptoms at time 

of remission 


Duration of 
remission 


remissions 


Subse()uent 


admission 










B. 1 


4400 


10 mos. 


2 wks. 







Pr. 1 ... 


2980 


12 " 


10 mos. 


0? 


1 


Bu. 1.... 


2300 


12 " 


6 wks. 





3 


Bu.2 


2200 


18 " 


4 mos. 


1 


2 


Bu. 3.... 


1400 


24 " 


4 wks. 




1 


Bu. 4.... 


1500? 


2S " 


4 wks. 


3 





M. 1 


1500 


12 " 


41 mos. 


2 





A. 1 


1450 


9 " 


2.\ " 







Pr. 2.... 


1325 


24 " 


4 " -f 


1 




G 


1160 


? 


20 ■' -1- 







H 


800 


" 


7 " 








C 


600 


3 vrs. 


5 " 


9 





Bi 


550 


2 wks. 


8 " 









These cases do not indicate that transfusion led to prolonga- 
tion of the remission. In only three instances did it last over 
si.x months, whereas among 329 cases collected by Cabot " there 
were remissions of over si.x montbs in Ki.i. .\o relation be- 
tween tbe amount of blood given and tho duration of the re- 
mission is apparent. 

.1. The Ikirali-on of Life. — Tbirtecn of the patients receiv- 
ing transfusion arc now dead, four are alive, while the remain- 
der could not be traced. The total individual duration of 
life from the oiuset of symptoms was as sliown in Table VII. 

Although this series i.s too small to serve as a basis for grou|) 
percentages it is clear that there was no demonstrable pro- 
longation of life in the cases in which transfusion was em- 
ployed. Patients treated by the elder general methods fre- 
quently live four years or longer. Thus, in (547 cases Cabot " 
found 7!' patients who lived over four years. Furthermore, it 
is noteworthy in this series that the patients living longe>t 
were not tlie ones in whom remission followed transfusion. 



May, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



lOa 



Four patients are still alive. The symptoms have been 
present one, two, two, and four years respectively. 

TABLE VII 



Patient 


Duration of life from 


Remission after 


onset of symptoma 


transfusion 


H 


4 vrs. 


None. 


W 


4 " 


None. 


H 


3A " 


None. 


C 


3J " 


Remission. 





3\ " 


Remission. 


M 


2 " 


Remission. 


D 


li " 


None. 


H 


U " 


Remission. 


M 


li " 


Remission. 


B 


1 " 


Remission. 


M 


1 " 


None. 


M 


10 mos. 


None. 


H 


8 " 


None. 



6. The Effect of Transfusion on Symptoms. — An analysis 
of the course of symptoms shows no definite variation in the 
groups of cases treated by different methods. In general, with 



one, death from pulmonary embolus occurred 19 days after 
operation. Si.\ of the remaining patients are dead. The data 
in these ca.ses are summarized in Table VIII. 

In no case was the clinical picture essentially altered, and 
no unusual prolongation of life occurred. Thus one patient 
lived two and a half years after splenectomy, and another 'is 
alive after one and a half years but very ill with recurring 
femoral phlebitis. In five cases transfusions were given during 
the period immediately following splenectomy. None the less 
in the four cases in which the length of the remission could be 
accurately determined symptoms returned after periods of 
three, four, four, and eight months, respectively. In one case 
there was no remission but progressive failure, in another post- 
operative death occurred from pulmonary embolus. The other 
two patients did not have the relapsing type of the disease. 
The height of the blood count cannot be regarded as remark- 
able, inasmuch as the patients were tran.sfused after operation 
e.xcept those not of the relapsing type. The.se cases fail to bear 
out the view that transfusions are " held " better after splenec- 



TABLE VIII 























a. 


"'■ 


W.. 


35 


P... 


62 


B... 


43 


A... 


38 


Bo. 


55 


S... 


25 


H.. 


67 


C. 


42 



1,700,000 3,600 27 

4,000,000 1,400 65 

3,100,000 60 

1,800,000 3,000 35 

2,800,000 5,300 93 

3,100,000 3,000 87 

2,9 0,000 10,400 58 



5 raos. 3,500,000 7,000 



3,500,000 10,400 70 

4,700,000 4,600 84 

0,000 6,000 72 

4,900,000 4,900 

3,900,000 6,800 100 

4,200,000 8,400 102 

2,100,000 31 



No remission. 



2300 
5000 



19 mos. 
2i yra. 
29 mos. 



5 mos. 
20 dys. 



Three subsequent remissions. Death 
from acute dysentery. 



Death in coma. 

Death in coma after rapid relapse. 



Prognessive cord changes. Death in 
coma after rapid relapse. 



Patient still living. 



Death, pulmonary embolus. 



* Direct transfusior 

the improvement in the blood, the symptoms referable to the 
anemia itself (dyspnoea, palpitation, dizziness, and weakness), 
and the gastro-intestinal disturbances were alleviated or dis- 
appeared. Fever regularly tended to fall and was rarely 
pre.sent on discharge in the patients who did well otherwise. 
Absence of relief of the central nervous system symptoms dur- 
ing the remission is well known. It was striking that trans- 
fusion also was ineffective in removing these disturbances. 
The disappointment of the patients was uniform in this re- 
gard, although in a few instances there was perhaps slight 
improvement. 

Splenectomy 
Although splenectomy for pernicious anemia is no longer 
done in this clinic, it seems of interest to report the late 
results. The operation was performed in 8 instances. In 



time of splenectomy 

tomy. In the four cases in which 4000, 5200, 2300 and 5000 cc. 
were given, the blood was not " held " at all by one patient, 
and in the others symptoms returned after three, three and 
four months, respectively. All these patients reacted to tran.s- 
fusion in essentially the same manner before splenectomy was 
done. Three patients showed marked spinal cord symptoms. 
In B., who had no marked anemia, " the spinal t^clerosis pro- 
gressed rapidly, although the blood was about .stationary until 
very near the end." In P. the cord changes progressed rapidly. 
Four months after operation he was unable to walk without 
crutches. Patient S. was admitted with absent knee-jerks, 
marked ata.xia, and impaired muscle sense. The blood count 
was 2,2G0,000, 3200, with 43 per cent Hb. After two months 
the count was 3,100,000, 3000, with 87 per cent Hb., all the 
symptoms had cleared up, there were no paripsthesias, and the 
knee-jerks were obtained. The treatment had consisted of 



10(5 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 327 



rest, diet, arsenic, and hydrochloric acid. Splenectomy was 
then performed. This patient's blood has remained fairly 
high ever since. He is alive after one and a half years. 

In summary, these cases furnish no proof that life was pro- 
longed, that remission was longer and more marked, that 
transfusions were better " held," or that there was any special 
relief of symptoms following splenectomy. 

Elimixatiox of " Focal Infectioxs '' 
Since the work of William Hunter, many writers have 
ascribed the picture of pernicious anemia to local " foci of 
infection." This doctrine has come especially to the front in 
the last few years largely owing to the studies of Billings " 
and his co-workers. That the association of these foci with 
pernicious anemia is a causal one is not, however, as yet proved. 
It seems that one should be very cautious in assuming an 
etiological relationship between a di.sease picture so clear cut 
and running such a typical course as pernicious anemia and 
lesions of such frequent occurrence as periapical abscesses, 
infected tonsils, and other local " foci of infection." The 
anemias knonni to be due to infection such as those occurring 
in septic diseases are of the simple secondary type and clear 
up when the primary disease heals or is eliminated. It may 
be that less definite deleterious effects are exercised on the 
course of the disease by foci of infection without specific causal 
relationship. 

In 12 cases a thorough study of the nose, throat, sinuses, 
teeth, gastro-intestinal tract, and lower urinary tract was 
made for foci of infection and, when found, these were elimi- 
nated. All these patients finally received clean bills of health 
from the various specialists. Most of them were given trans- 
fusions and in one case splenectomy was also performed. In 
none was there any feature in the subsequent course to dis- 
tinguish them from the group in whicli foci were not found, or 
if found were not treated, either as to total duration of life 
or extent and degree of remission. 

It is unlikely, therefore, that such foci of infection are the 
cause of pernicious anemia, although it seems wise to treat 
them for their own sake as well as for any possible general 
beneficial effects which may follow. 

Conclusions 

An effort has been made to analyze the results of treatment 
in these cases from a purely objective point of view. Ciiniial 



impressions have been disregarded, and no attempt has been 
made to promote or discredit any particular therapeutic 
measure. It should be recognized that such statistics lead to 
only general conclusions which allow of exceptions in indi- 
vidual cases. The results may be summarized as follows : 

1. Xo definite evidence has been found that either trans- 
fusion, splenectomy, or elimination of foci of infection pro- 
longs the life of patients suffering from pernicious anemia. 

i. Transfusion performed at a time when the patient was 
not refractory brought on remission in about half the cases, 
and enabled the blood count to be raised to a higher level than 
it reaches in cases not so treated. 

3. Such artificial plethoras did not increase the duration of 
the remission, although the patients usually had a sense of well 
being while the count was high. 

4. At other times the same patients were refractory to trans- 
fusion as well as to other methods of treatment. 

5. The central nervous system symptoms were as little bene- 
fited by transfusion and splenectomy as by other methods of 
therapy. 

6. Transfusions of blood were not " held " better after 
splenectomy than before. 

REFERENCES 

1. Ottenberg, R., and Libruan, E.: Amer. Jour. Med. Sc. 1915, 
CL, 36. 

2. Archibald, Alexander: St. Paul Med. Jour., 1917, XIX, 43. 

3. Larrabee, Ralph C: Boston Med. and Surg. Jour., 1917, 
CLXXVI, 553. 

4. Barker, L. F., and Sprunt, T. P.: Bull, of The Johns Hopkins 
Hosp., 1917, XXVIII, 355. 

5. Meleney, Henry E., Stearns, Wilbur \V., Fortuine, Stanley T., 
Ferry, Roland M.: Amer. Jour. Med. Sc, 1917, CLIV, 733. 

6. Lee, Roger I., Vincent, Beth, and Robertson, Oswald H.: 
Jour. A. M. A., 1915, CXV, 216. 

7. Krumbhaar Edward B.: Jour. A. M. A., 191G, CXVII. 723. 

8. Minot, G. R., and Lee, R. I.: Boston Med. and Surs. Jour., 
1917, CLXXVI I, 761. 

9. Giffin, H. Z.: Jour. A. M. A., 1917, CXVIII, 429. 

10. Lee, Roger I., Minot, Geo. R., and Vincent, Beth: Jour. 
A. M. A.. 1916, CXVII, 719. 

11. McClure. R. D., and Dunn, G. R.: Bull. Johns Hopkins Hosp., 
1917, XXVIII, 99. 

12. Sydenstricker, V. P. W., Mason, V. R., and Rivers, T. M.: 
Jour. A. M. A., 1917, CXVIII, 1677. 

13. Cabot, R. C, in Osier & McCrae's Modern Medicine, 1915, IV, 
p. 619. 

14. Billings. Frank: Focal Infection. Appleton. 1916. 



TOBACCO 8M0KE AND PULMONARY TUBERCULOSIS 



J'>v .\lli:n K. Khaisk 



This study ' may strike many as having turned out " against 
the rule." But to some of us its results are not unexpected. 
Major Webb finds, in effect, that comparatively few non- 



* Elaboration of remarks made in a discussion of a paper, " The 
Effect of the Inhalation of Cigarette Smoke on the Lungs. A Clini- 
cal Study," read by Major Gerald B. Webb before the Laennec 
Society of The Johns Hopkins Hospital, February 25, 1918. 



smokers (only 21 per cent) have rondii, while nu)st smokers 
do exhibit these signs of chronic bronchial irritation, and 
cigarette smoke inhalers almost invariably show them (S;5 per 
cent). He finds further that of a comparatively large body of 
young men (over 3000), the proportion that was discharged 
from active army .«crvicc because of active tuberculosis was no 
higher among the smokers, the men who had ronchi, than 
Minoiig the non-smokers with relatively " quiet " chests. 



Mat, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



107 



Eonchi are indications of bronchial irritation and a conse- 
quent inflammation ; and it might have been predicted that 
individuals who are habitually subjecting their respiratory 
tract to the far-from-soothing influence of cigarette smoke 
would be more likely to exhibit its effects, that is, inflamma- 
tion, than those whose gaseous intake is confined to the more or 
less undefiled atmospheric air of town and country. This side 
of Major Webb's study represents, therefore, no startling dis- 
covery. But its other result — that the " ronchous " smokers 
acquaintance with the tubercle bacillus is just as favorable and 
just as well guarded as that of his non-smoking neighbor — 
embodies certain implications that run so counter to what we 
have been taught and what we have comfortably believed, that 
it perhaps deserves a little more than a word of notice. 

We were once told that in our struggle against the tubercle 
bacillus it was of great importance that we avoid anything 
that would bring about irritation of the respiratory tract. 1 
believe that much of the antituberculosis propaganda still 
recites that inflamed conditions of the nose, throat, larynx 
and bronchi lay us more open to tuberculous infection. The 
old admonitions had it that the inflammations brought about 
by the common cold, catarrh, tobacco, etc., left us in a " run 
down" condition and therefore comparatively defenseless 
against bacillary invasion. The idea undoubtedly had its 
birth in the long-noted and indisputable fact that the common 
cold and other catarrhal conditions were frequently followed 
by outbreaks of pulmonary tuberculosis. Therefore, the local 
inflammation was favorable and nourishing soil for the im- 
plantation of tubercle bacilli and a host of other microorgan- 
isms. This was a very natural presumption. For an inflamed 
tissue is a diseased tissue and without examining the matter 
more closely it seems reasonable to presuppose that a diseased 
tissue is more open to infection — to bacterial implantation 
and invasion — than a healthy tissue. 

But let us analyze these matters further. In another place 
I ' have already pointed out that it is at least debatable whether 
inflammation leads to increased susceptibility to bacterial 
infection. Clinical data at once belie this assumption. If the 
proposition is maintained, then I would at once ask questions 
something as follows: Why are chronic leg ulcers so uncom- 
monly the seat of acute bacterial infection ? Why is erysipelas 
more often seen to arise in the healthy non-inflamed skin or 
in the clean, operative wound than in the epithelioma ulcer 
or in the open patch of lupus where we should look for it ? 
Why is a story of frank, acute bronchitis ushering in acute 
lobar pneumonia unusual ? 

In this connection too I have elsewhere called attention to 
what Opie" has to say on the function of inflammation. 
" Views concerning the nature of inflammation," he writes, 
" are widely diverse, but all are agreed that inflammation 
accomplishes the destruction and solution of a variety of 
substances, and notably those proteins which form the bodies 
of parasitic invaders." In the same lecture Opie cites experi- 
mental evidence as follows ; " Pawlowsky has demonstrated 
the presence of staphylococci in the blood and organs of 
guinea-pigs from 24 to 48 hours after inoculation of the knee- 



joint, but has been able to show that dissemination is inhibited 
or wholly prevented if, before inoculation, acute inflammation 
of the joint has been produced by the injection of some sterile 
irritant, such as turpentine, alcohol or solution of quinine." 
And again, " Issayeff .... showed that the peritonitis in- 
duced by a variety of sterile irritants, such as a foreign blood 
serum, bouillon, or normal salt solution, temporarily increases 
resistance to subsequent intraperitoneal inoculation of 
bacteria." 

Xow what does all this mean ? It must at least suggest that 
inflammation is the visil)le expression of an animal organism's 
capacity to react to irritation (whether the irritation be me- 
chanical, chemical or thermal ; whether it be set up by organ- 
ized or unorganized material, by inert or living substances, by 
grains of sand or bacterial parasites), and that this reacting 
capacity is a true resisting function of tissues. It is an effort 
on the part of tissue to defend itself, to limit the assault of 
the invader, to wall off the offending irritant. If this be true — 
and to me it hardly admits of any doubt — we must give up our 
ideas that inflamed tissues are especially favorable soil for 
bacterial invasion. They are the very reverse : they are points 
of unusual resistance. 

It would be perfectly useless to speculate as to what element 
in the inflammatory process brings into the struggle the re- 
sisting units or substances — as to whether the serum, or the 
leucocytes, or the new proliferatipn of fixed cells renders the 
invaders impotent. That is material for studies of another 
nature. The point I want to make here is that the animal body 
interposes a something, a barrier, if you will, between itself 
and parasites that are trying to gain a foothold ; and that the 
subsequent fate of the animal will depend largely on the com- 
petence and integrity of this barrier. In what this competence 
consists is another matter that is not at present germane. 

It is because of considerations like these that some of lis 
have begun to doubt the soundness of the view that looks upon 
an inflamed spot as a locus minoris resistentice for infection 
by microorganisms. But what we haVe to say applies only to 
the incident of becoming infected, not to what may or may not 
happen to a focus of infection that is already established. 

It seems to me that it is not suflBciently well recognized, or, 
at least, not emphasized enough, that the factors that favor 
or prevent the implantation of an infection need not be at all 
similar to those that favor or prevent the spread of an infection, 
once it has taken place. This point is beautifully illustrated 
in an infection that tends to focalize like tuberculosis. In 
general, we can say that relative stasis is favorable to infection, 
but less likely to promote the spread of tubercle, while relative 
movement is likely to prevent localization of bacilli, but more 
prone to spread tubercle once the bacilli have focalized ; that is, 
other factors like the numbers of bacilli and the character of 
the respective tubercles being equal. We find, therefore, that 
infection of the lung with tubercle bacilli is much more com- 
mon at the apex where movement (of lung, of air current and 
of lymphatic flow) is relatively small, than lower down and 
towards the front where movements are comparatively great. 
It is the rule for first infections to occur toward the tops and 



108 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 327 



posterior surfaces where movemeuts are relatively restricted 
by less yielding structures, as compared with the more expan- 
sile front and bottom of the thoracic cage. Similarly, pleural 
adhesions arc in general much more abundant and of much 
greater extent above and in back than in front and below : and 
when they do occur in front and below they are likely to lie 
attached to the ribs which are more fixed than the intercostal 
spaces. 

Now, though first infection prefers the top and back of the 
lung, the tubercle that results therefrom is much more likely 
to reach quiescence and arrest than if infection takes place in 
the more movable parts of the lung. Even when tubercle 
formation has l)econie extensive we Ijecome much more con- 
cerned about the formation of what we might call mid- 
pulmonary disease than about the same amount of apical dis- 
ease. Clinical experience has taught us that in the former 
case we are dealing with a more serious condition than in the 
latter ; and one of the reasons for this is that, as compared with 
relative inactivity, movement favors the mobilization and 
spread of focal products. 

I have touched on this matter of the effects of movement 
and inactivity on two contrasting and different phases of 
tuberculosis, namely, infection and metastasis, because I want 
to protest against the confusion that usually involves any dis- 
cussion of tuberculosis, when, as generally happens, it i-^ 
assumed that what holds good in reference to the taking place 
of infection also holds as concerns its further development and 
spread, and when, as so often happens, the factors that govern 
therapy are mixed up or made identical with those that relate 
to prophylaxis. And T am further desirous of pointing out 
how inflammation can have two very different effects, depend- 
ing on whether it is concerned with implantation of bacilli 
or an action on a focus already present. 

As regards im])lantation, my argument has already laid it 
down that microorganisms that are brought to a tissue that is 
already inflamed fall on relatively resistant soil. But as re- 
gards the further development and spread of an already estab- 
lished focus, inflammation can exert an effect that may not 
be so favorable. Tubercle anywhere in the body is benign or 
innocuous just so long as its investing envelope is of such a 
nature that it is so impervious to the circulation of tissue 
juices that goes on between it and the host that the maximum 
amount of material absorbed is not enough to produce symp- 
toms of intoxication in the host and the nuiximum of the 
kinetic energy of the circulation is not sufficient to mobilize 
bacilli and spread them. As sclerosis of tubercle proceeds, the 
interior of the formation becomes more and more shut off 
from the surrounding tissues. Xow, anything that can bring 
about a better circulation around this avascular struclure. 
anything that will promote an enhancet! give and take between 
it and the surrounding tissue, will tend to '' unlock '' or " open 
uji " this walled-in structure. Among other things this is 
exactly what inflammation — hyperaMuia, congestion, etc. — can 
do and frequently does do. .\nd when it does this then inflam- 
mation becomes a contributory and inciting factor to the 
development of tuberculosis: not, remember, to infection with 



tubercle, but to the spread of tubercle, or the development of 
tuberculosis. Here then we can look upon inflammation as 
we viewed movement — as capable of exerting two very different 
and antithetical effects, depending on whether we are con- 
sidering either of two very different phases of what in the large 
is one problem. 

Let us now come back to ^Major Webb's paper and the 
immediate questions that its subject matter raises. !Major 
Webb fuids that men with bronchi in a state of chronic inflam- 
mation do not develop the disease tuberculosis in larger pro- 
portions than men with what might be called more normal 
bronchi. The older view was that inflammations of the respira- 
tory tract do.predispose to tuberculosis, and I believe that many 
assumed that this predisposition was a predisposition to in- 
fection. To-day, with our newer knowledge of the relative 
incidence of infection and morbidity, few of us, even without 
going into the matter further, would believe that, if men with 
inflamed throats and bronchi fell ill with tuberculosis, this 
disease was the result of recent infection. We should be more 
inclined to believe that the disease represented the awakening 
of old quie.scent tubercle, planted perhaps years before. There- 
fore, on this basis alone, we should say that irritation of the 
upper respiratory tract in an adult played no part in infection. 
But we have in addition pointed out that inflammation, if it 
does anything, probably resists a fresh infection. 

Now, if it were granted that inflammation does not lay a 
tissue more open to infection, but that on the contrary it 
probably plays a part in resisting bacterial invasion, it still 
remains for us to consider what effect constant irritation, 
brought about perhaps by some such stimulus as tobacco smoke, 
might have on foci of tubercle that exist in tissue. This set 
of circumstances would no doubt represent what more likely 
occurs under natural conditions : that is, some tubercle is 
already present in the lungs of individuals who take up the 
smoking and inhaling habit, and it is this tubercle that later 
blazes out into clinical disease, and again, therefore, it is this 
tubercle on which the inhaled cigarette smoke exerts an effect. 

It will immediately occur to every one that if nearly every- 
body has quiescent tubercle and if inflammation can exert an 
awakening influence on such dormant tubercle and if fre- 
quently the ultimate result of the iiiliiilatiim of cigarette 
smoke is a chronic bronchial inflannnation. then why do not 
more cigarette inhalers develop tuberculosis? The answer is, 
that the factors are not so simple as this qualitative statement 
of the problem. To go a little further we nnist deal with the 
quantitative phases of the situation. 

It is not to be doubted that while just enough and perhajis 
too much inflammation is bad for a tubercle, a little bit of 
inflammation either exerts no deleterious effect on it, or may, 
indeed, be good for it. We see this exquisitely exemplified in 
studying the influence of tuberculin on foral tubercle. All of 
you are aware that if sufficient tuberculin gets to a I'liiiis of 
tubercle it will cause the lattor to react with inflammation. 
If now the focus is not too large, is not too much of the nature 
of a diffuse jirocess and is well enough invested to begin with, 
and if the inflammation is not too intense, we may observe (at 



THE JOHNS HOPKINS HOSPITAL BULLETIN, MAY. 1918 




BORN SEPTEMBER 2S. 1862. DIED NOVEMBER 17, 1917 



May, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



109 



least, experimeutally) the most amazing results to follow tiif 
focal reaction, that is, inflammation. In a short time such a 
focus that may have persisted for weeks and mouths may dis- 
appear like snow before the summer sun, while non-reacted, 
non-inflamed foci in control animals go on to necrosis and dis- 
semination. But too violent au inflammation in too acute a 
patch of tubercle can cause irreparable damage from the tissue 
death and spread of the process that it can bring about. 

In the tobacco smoke inhaler we have a comparatively mild 
irritation, repeated often over a long period. What results is 
likely to be a chronic inflammation of a low grade. Everything 
else being equal, its net effects on tubercle that is otherwise 
being well taken care of should be mildly " stimulating " and 
tending to repair ; not violently upsetting, as might occur from 
a lobar pneumonia in the area surrounding the tubercle. We 
should expect, therefore, that a number of divergent and per- 
haps opposing factors would balance one another, and that, as 



compared with one thousand non-smokers, a thousand smokers 
would reach equilibrium. 

What I have said applies only to the. local irritating effect 
of tobacco smoke. This effect is to be kept altogether disso- 
ciated from any discussion of the constitutional effects of to- 
bacco. Constitutional effects, such as the influence of tobacco 
on digestion, on the nervous system, on the vascular system, en 
the psyche, undoubtedly come into play and would have to be 
reckoned with in any broader discussion of the influence of the 
use of tobacco on the development of tuberculosis in general. 

REFERENCES 

1. Webb, Gerald B,: The effect of the inhalation of cigarette 
smoke on the lungs. A clinical study. Am. Rev. Tub., 1918, II, 25. 

2. Krause, A. K. : Cellular or tissue immunity to tuberculosis 
and its relation to the pathology of tuberculosis. Nat. Asso. Study 
and Prev. Tub., Tr. Twelfth Annual Meeting, 1916, 243. 

3. Opie, E. L.: Inflammation. Arch. Int. Med., 1910, V, 541. 



MEMORIAL SERVICES IN HONOR OF FRANKLIN PAINE MALL, 
PROFESSOR OF ANATOMY, JOHNS HOPKINS UNIVERSITY, 

189:^ TO 1917 



A memorial meeting in honor of Dr. ilall was held on Sun- 
day, February 3, 1918, at i p. m., in the hall of the Civil 
Engineering Building at Homewood. Addresses were made 
by President Frank Johnson Goodnow, of the University; 
President Eobert S. Woodward, of the Carnegie Institution : 
Dr. William H. Welch, director of the School of Hygiene and 
Public Health of the University; Dr. Lewellys Franklin 
Barker, professor of Clinical Medicine in the University; Dr. 
Simon Flexner, director of the Eockefeller Institute and 
Dr. Florence Rena Sabin, professor of Histology in the 
University. 

President Frank Johnson Goodnow. — We are assembled 
here to-day to honor the memory of our lamented colleague 
and friend, Dr. Mall. Dr. Mall had been up to the time of his 
death continuously and uninterruptedly as.sociated with the 
medical school from the time of its opening. He was one of 
the group who a quarter of a century ago inaugurated a new 
venture in medical in.struction in this country. The purposes 
which were then outlined, the ideas which were then enter- 
tained, the methods which were then adopted had subsequently 
a widespread influence throughout the land. It is somewhat 
difficult for us, separated as we are by .so long a period from 
the original time of their formulation and accustomed as we 
are to the changes which they caused, to appreciate how novel 
and how important was the work then undertaken. 

For the success attendant upon the medical .school. Dr. ilall 
was in no small measure responsible. A brilliant and tireless 
investigator, be made invaluable contributions to the science to 
which he devoted him.self and won prestige for the institution 
with which he was connected. A wise and sane counselor, he 
exercised a potent and salutary influence over the policy of the 
medical faculty. A kindly and courteous gentleman, he greatly 
endeared himself to his cojleasjues and as.^ociates. 



Passing away in the prime of life and at the height of his 
powers he leaves in the world of science a gap which it will be 
difficult to fill, and among his friends a sense of loss which it is 
impossible to overcome. 

We have, however, the satisfaction of knowing that the 
university, of which he was a member, is better and finer for 
what he was and did. His life and work will long continue to 
be an inspiration to the colleagues he has left behind and to the 
students whom he taught. 

President R. S. Woodward, Carnegie Institution, Washing- 
ton, D. C. — My acquaintance with Professor Franklin Paine 
Mall began about 20 years ago. We had met casually at 
that national center of biological interest. Woods Hole, and 
elsewhere, at frequent intervals diiring the decade and a 
half which preceded the more intimate association which 
began in 1913 and continued with increasing intimacy and 
attraction until the time nf his deatli. During the year 
1912, and especially near the end thereof, a number of con- 
ferences were held with him looking to the establishment on 
a permanent basis, under the auspices of the Carnegie Insti- 
tution of Washington, of the researches in embryology to 
which he had long given attention. The conferences re- 
ferred to and the more intimate relations which followed in 
the succeeding years brought about a degree of contact and 
sympathy which enabled us to understand one another to a 
degree rarely attainable. This experience has been especially 
interesting and instructive to me, and there appear to be the 
best of reasons to assume that it was similarly interesting and 
instructive to him. From its inception Professor Mall applied 
his unusual capacity for interpretation of the minds of men to 
me, and he appeared to be equally con.scious of the fact that I 
endenvored also to make a special study of liini and his char- 



no 



JOHNS HOPKINS HOSPITAL BULLETIN 



[Xo. 327 



acteristics. I am uot aware that he made any record of his 
observations upon me ; there was no occasion for him to do so ; 
but the untimely termination of his terrestrial career and the 
present memorial occasion seem to render it permissible to 
make acknowledgment of, and to record here, the impressions 
he produced upon me. 

Since my association with Professor Mall had much to do 
with purely business affairs, in the development of his depart- 
ment of research, it is not improper to speak of his business 
abilities, although the world at large would probably not 
credit him with the possession of noteworthy capacity for 
fiscal affairs. There is, indeed, still, even in the twentieth 
century, a widely spread belief that men who are devoted to 
the pursuit of science, or to activities whose results are not 
measured in dollars and cents, are conspicuously lacking in 
business capacity. But this is a fallacy tvhich will disap- 
pear under a closer study of the fundamentals essential in the 
effective conduct of affairs. It is commonly held, particularly 
in government circles, that those only possess executive ability 
who are trying to exercise it. Thus it is possible for one who 
has few qualifications essential to effective conduct of affairs 
to derive credit for remarkable capacity in such work, especi- 
ally if he be able to depend upon subordinates to prevent him 
from going wrong. On the other hand, it is often said that 
executive ability consists in doing well what ought not to be 
done. But it would be wiser to say that executive ability con- 
sists in doing well and without ostentation anything that is 
worth doing. In this better sense of the phrase Professor 
Mall excelled. He possessed uncommonly clear vision. Ho 
held adequately considered theories of procedure, and he en- 
tertained a rational perspective of the relative importance 
of the factors involved in any case. He possessed all the ele- 
ments, therefore, of superior capacity for the ordinary affairs 
of life, although he was never called upon to concentrate his 
attention exclusively on them. 

His life was given rather to research, and his theory and 
practice therein are deservedly worthy of special attention. 
He held very distinct views on this subject. He understood 
. very clearly that progress, resulting from research, does not 
consist simply in innovation, much less in eccentricity. He 
understood, likewise, that progress does not consist in the 
mere accumulation of facts in accordance with well-known 
methods. He had no fear of breaking with precedent. His 
criticisms were sometimes mistaken for iconoclasm ; but while 
they were often destructive, they were also, in general, highly 
constructive. He was exceedingly fertile in suggesting better 
ways of doing things even in matters which lay outside his 
special interests. Whatever entered his mind was visualized 
in a variety of aspects. He was surprisingly quick in sepa- 
rating the essentials from tlie unessentials of any question 
presented to him. 

Of his work in science, I am not qualified to speak except 
in general terms. He was a specialist in certain branches of 
biology, and in these he developed processes peculiarly his own. 
But in their general aspects his methods are the well known 



methods of science, and one does not need to know much of his 
technique to discover the reasons for his remarkable capacity 
for productive work. His sincerity, his industry, and his 
comprehensive knowledge of his work carried with them con- 
viction and confidence. He entertained always a clearly defi- 
nite plan for any piece of work, having set items in his program 
for every step from the initial observations, investigations or 
data, to the final publication of the results and the distribution 
of them to experts who might be expected to appreciate and 
hence to make effective use of them. He understood uncom- 
monly well the value of system ; but he never permitted the 
mere machinery of research to absorb his attention or to deflect 
him from his principal objects. He made extensive use, for 
example, of card catalogues and bibliographies but always as 
means to rather than as ends in his investigations. 

Professor Mall possessed certain notable characteristics 
which were manifested in striking fashion often m confer- 
ences with him concerning subjects of special mutual interest. 
He was a man of few words, he was never prolix in argument, 
and he knew well when a conference was finished. He was 
able always to concentrate attention on the salient features of 
a subject under discussion. He was extremely reasonable with 
respect to matters of controversy and this made it a source 
of pleasure to confer with him even when differences not 
easily dissipated arose; for his manifest desire to have the 
adjustment of every question depend on its merits was always 
an assurance that the right conclusion would be ultimately 
reached. 

Summarily characterized, Professor Mall was an ideally 
typical man of science. He tried to visualize the universe as 
it is; or, in more common parlance, he looked at, and sought 
always to see, things as they are. His perception of reality 
and his conformity to it were noteworthy in all his activities. 
He was able to see much more clearly than most of us that 
limitations exist on every hand. Men of science, generally, and 
mathematicians even, are not infrequently found to entertain 
an inadequate respect for the rules of elementary arithmetic; 
but this is a defect of the human race rather than of any class 
of men, as is well demonstrated by tlie fact that professional 
financiers sliow least respect for those rules. But in an age 
when many good men have lost their heads, temporarily, at 
least, in respect to the possibilities of the ways and means 
available for promoting research and discovery, the equilibrium 
of Professor ]\Iall remained undisturbed. His foresight was 
singularly free from the fogs and the illusions wliich often 
diminish the eflfieiency of enthusiastic investigators. He knew 
well how to count the immediate costs as well as to estimate the 
ultimate consequences of the researches to which he was 
devoted. 

Quite naturally and gracefully the mental (|ualities already 
alluded to were supplemented by correspondingly high moral 
qualities. The two kinds of qualities were, indeed, inseparable 
in him. They were neither stored in separate compartments 
nor restricted in use to separate days or occasions ; the entire 
man was always visible and available in his presence. Where 
he stood, or what he thought with respect to any question to 



May, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



111 



which he gave attention was never a matter of doubt. He 
faced his colleagues with the same frankness and the same 
truthfulness with which he approached the problems presented 
by his favorite science. It is in this rare combination of 
mental and moral traits that we find the foamdations at once 
for his signal success as an investigator and for the affectionate 
and abiding regard he won from all those who had the good 
fortune to share in his more intimate friendships. 

Dr. William H. Welch (Abstract).'— Dr. Welch outlined 
briefly Dr. Mall's medical training and the steps which led 
him to the laboratories of His and Ludwig in Leipzig, where 
he and Dr. Welch first met in the winter of 1884-85. Speaking 
of the great influence which these two men had upon his scien- 
tific development, Dr. Welch said : 

Ludwig's was, I believe, the stronger and more personal one; 
that of His was more in methods and the specialized problems ot 
embryology. I had worked in Ludwig's laboratory 10 years before 
and he often spoke to me rather freely. I doubt if he ever had a 
student to whom he was more attached, or who had made a more 
profound impression upon him that Mall. He more than once 
spoke to me of Mall's remarkable intellectual qualities. 

At that time Dr. Welch had already been called to The 
Johns Hopkins University, and upon his return to America 
he received a letter from Dr. Mall expressing a desire to come 
here and work. In consequence he came to Baltimore in 
188C as fellow in pathology. 

Wliile in the pathological laboratory he was, as you may imagine, 
an independent worker; it was a delight to have him there. He 
assisted in the course in bacteriology, and his methods then had 
the same originality that has always characterized them. He 
was interested in connective tissue and discovered that certain 
varieties of bacteria had the power of digesting certain kinds of 
connective tissue. 

At the end of three years he went with Professor Stanley 
Hall to Clark University, and later to the University of Chi- 
cago. He had made the acquaintance of President Harper 
while in Leipzig, and the two were close personal friends. It 
was with some misgivings, therefore, that Dr. Welch, at 
the request of The Johns Hopkins University, set about to 
induce Dr. Mall to return to Baltimore at the opening of the 
medical school in 1893. The plan of the school, however, 
appealed strongly to Dr. Mall, and although every effort was 
made to keep him at the University of Chicago, he accepted the 
new post. Of his work here Dr. Welch said : 

Mall belonged to the group made up of those men who came 
in the early days of the hospital, in 18S9, and those who came 
as workers in the scientific laboratories of the new medical school 
in 1893. He is the first of that group to be taken away. I think 
my colleagues will agree that, of all that early group, he was the 
most productive contributor to science and one of the most stimu- 
lating influences. There is no expressing the loss which this 
school and university, and we, his colleagues, have suffered. He 
was wise and sound, and had a great insight into the value of 
things. I know of no one whose powers of mind were more pene- 



' Owing to the continued absence of Dr. Welch in connection with 
his work in the office of the surgeon-general of the army, it has 
not been possible to give his address in full. 



trating. He, more than any of us, perhaps, represented two of 
our educational ideals — freedom in teaching, freedom in learning, 
freedom of the teacher, freedom of the student. Indeed I may 
say that President Oilman, having once selected a man whom 
he considered qualified as the head of a department, left him a 
pretty free hand. Mall entered into that spirit most thoroughly, 
and was undoubtedly a very inspiring influence for the better 
students. That was one of the ideals he stood for. The other was, 
that the primary qualification of a preceptor should be the capacity 
to produce or to stimulate production. These two ideals he never 
lost sight of, and in him they were exemplified to a surprising 
degree. 

He was to all of us a delightful companion, and it was a joy 
to be with him. He was attractive and had a whimsical way of 
saying things, but he was very wise. He ranks with Rowland as 
one of those men who have added lustre to the university by 
their contributions to science, and who, by their revolutionary 
Influence upon their subjects and their great capacities as teachers, 
have led others to become teachers. One has only to consider what 
anatomy stands for in our medical schools to-day, as compared 
to what it was when Mall began his work, to appreciate what his 
influence has been upon the science of medicine. His memory is, 
indeed, one of the most precious possessions, not only for us, his 
colleagues, friends and admirers, but for all times of this 
university. 

Dr. Lewellys Franklin Barker. — Adequately to present the 
personality of Franklin Paine Mall, to describe the essential 
qualities of his character, and to do Justice to the distinctive 
excellences of his intellect, would require the pen of an expert 
psychographer, the selective ability and the power of artistic 
comjiosition possessed only by a skillful naturalist of souls. 
It is to be hoped that, sometime, an experienced practitioner 
of the art may supply us with the fair and right account that 
we should like. Those of us — pupils, colleagues, and friends — 
that are gathered to-day at this memorial meeting can scarcely 
do more than contribute materials and clues that may later 
on be an aid to the definitive production that will be pro- 
portionate and satisfying. 

No one who enjoyed close association with Mall during his 
25 years professorship at The Johns Hopkins Medical School 
could fail to recognize a unique personality, whose significance 
for medical science and especially for anatomy in this country 
was outstanding ; and those who were admitted to the circle 
of his friends counted the experience as one of the most re- 
warding and precious of the privileges of their lives. For 
some five years it was my good fortune to be his assistant in 
the anatomical laboratory here, and, seeing him daily in his 
work, I had manifold opportunity to become impressed with 
his powers and his activities as investigator, as teacher, and as 
educational reformer; and, above all, I came to know him as 
a man and a friend. Concerning his work as an anatomist 
Professor Sabin is to speak; I shall refer to his anatomical 
work only in as far as it throws light on the intellect and 
character of the man. 

Jlairs greatest professional interest lay in the promotion of 
original research in anatomy and especially in human embry- 
ology. His appetite was whetted for the pleasures of the in- 
tellect. He enjoyed accumulating facts but he longed still 
more for that most exalted of intellectual pleasures — the dis- 
covery of truth. He had an inexhaustible enthusiasm for the 



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[No. 327 



study of form and particularly for inquiries into the genesis 
of form. He delighted in finding (and fixing in enlarged 
reproductions that are permanent records) the several stages 
through which the body, or a part of the body, passes from its 
first formation in the embryo onward toward complete devel- 
opment. In his opinion, not much progress in human anatomy 
can now be expected from mere dissections of the adult human 
body; advances in our knowledge of human structure can 
come only by way of microscopic and chemical studies of the 
parts or by investigations into the genesis of the organs ami 
tissues of man and animals. An institute that attempts fairly 
to represent the subject of anatomy must, of course, be ine- 
pared to teach and to study the mature body of the highest 
animal form, but it must also, he thought, concern itself 
largely with the origin and development of the indivi(hial 
being (ontogeny) and with the racial evolution of the tyiic 
(phylogeny). Though his own interests lay more in embryo- 
logical than in comparative anatomical inquiry, he had a 
deep sympathy with both modes of attack and was ever 
ready to encourage researches in either direction. His atten- 
tion was early drawn to pathological human embryos ami 
throughout his life he collected these as well as normal forms 
and subjected them to intensive study by the newer metlio(l>. 
Though predominantly a student of form, he was by no means 
insensible to the delights and the reward.* of the study of 
functions; indeed a number of his researches were directed 
toward the solution of what might be designated physiological- 
anatomical problems, such as the determination of the func- 
tional-structural units in the liver and of the vascular sujiply 
of the several viscera. The influence of the teachers that in- 
spired him — Welch in pathology, Ludwig in physiology and 
hi.stology, and His in embryology and histogenesis — was evi- 
dent in the directions that his work took, but his jicriod of 
tutelage was brief, his problems were his own, and he will 
always be distinguished as one of the independent thinkers ami 
investigators of our time. 

His method of teaching was unusual, lie raicly. if vwv. 
lectured. Not that he thought the lecture of no didactic value ; 
on the contrary, lie was a firm believer in its .stinuilating elTeit 
when properly prepared, illustrated and delivered. But lu' 
felt that he himself could tcacli better in other ways, and lie 
relegated the lectures to other members of his department. 
He was, however, a master of what is called " elbow-teaching,"' 
and no student who has ever been at his elbow will ever forget 
the cliaracter of this relationship — his trenchant comments, 
liis'startlings of the intellect and emotions, his humorous ami 
sometimes satirical thrusts, and, above all, his earnest and 
sincere desire to make the neo])hyte an independent worker. 
Xew students often failed to understand him. .Vccustonied 
in the college of liberal arts to lucid exposition, to measured 
tasks of memory, to recitations on text-book n'iuling. uml tn 
the performance of laboratory work so carefully plinined and 
described as to leave but little room for personal initiative 
or for independent thought, many of the freshmen in the medi- 
cal school felt " lost " when they were told by the profe.s.'ior 
in his white gown to begin the dissection of a part, usnig atlas 



and text-book as guides, without any sjjecial instruction as to 
where or how to begin, without description of what was to be 
observed, and with no intimations that definite amounts of 
work should be performed in given spaces of time. Of course, 
they floundered, and often they bitterly complained. The 
method was drastic, and some, I fear, never understood its 
purpose. For most students with good natural endowment, 
however, the compulsion to realization of the fact that on 
entrance to the medical school the period of spoonfed education 
was over and that the time for acquiring the power to work 
more independently had arrived, though abrupt and perhaps 
painful, was most salutary, and I have heard many a student 
admit that he owed to Mall's method his intellectual awak- 
ening and his first arou-sal of desire to become an independent 
scientific worker. Mall's contempt for slovenly or di.shonest 
work, his admiration of a rigidly jjerfected technique, his 
encouragement of objectivity in study, his insistence upon 
familiarity with the bibliographic sources, his emphasis iipon 
the duty and pleasure of extending, rather than upon merely 
acquiring, knowledge, his impatience with inaccuracy and with 
stupidity, his unswerving loyalty to the highest ideals of 
natural science — all were qualities that made him a working 
companion of inestimable value to the young men and women 
who entered The Johns Hopkins Medical School. His in- 
fluence upon the rank and file of the students, large and bene- 
ficial as it was, was even exceeded, however, by the effect he 
had upon the small group of more original minds in each 
class and upon the members of his staff, ilall had a nose for 
the potential scientific investigator. With almost unerring 
accuracy he would scent out young talent and give it special 
encouragement and opportunities. Not all buds, it is true, 
opened in that atmosphere — a number have found conditions 
more favorable to the unfolding of their special talents in 
other departments later in the course — but it is interesting in 
looking over the scientific publications of graduates of our 
medical school to note how many of their authors began to 
evince an interest in original inquiry while in the anatomical 
laboratory. It was largely owing to flail's early capture of 
promising young minds that so many have found a career in 
anatomy interesting and satisfying, and that a large number of 
the cliiiirs of anatomy in American medical scliools are now 
tilled by his ]iupils. .\ still larger number who were led by 
him to undertake original inquiry have continued to be scien- 
tifically productive in other fields of medical .science, pre- 
clinical and clinical. It was a principle with ilall that any 
de)iartment in a university .should teach its subject for its 
own sake, without too much concern for its application to the 
work of lii-anches to be pursued later in the .student's course. 
He maintained that it was not the business of the department 
of anatomy to teach the so-called surgical and medical applied 
anatomy, for these subjects properly belong, he asserted, to the 
departments of surgery and medicine. From this position he 
ciinid not be budged, either by the imprecations of clinicians 
or the threats of State Board Examiners. By his own special 
methods of teaching, however, and with the aid of a carefully 
selecte<l and well-organized teaching stafl", he fulfilled the 



May, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



ii;{ 



fuuetiou of a university teacher, for he saw to it, first, tliat 
undergraduates secured a knowledge of tlie main facts and 
principles of his science and some acquaintance with its 
practical-technical methods of investigation ; and, secondly, 
that numerous workers were indiiced to pursue anatomy as a 
career, devoting the rest of their lives and energies to the teach- 
ing of the subject and to original inquiry in some one of its 
divisions. 

Though the character and intellect of the man are well 
revealed by his activities as investigator and as teacher, it 
would be remiss not to speak of his ability as organizer, and 
of his wisdom as counsellor and educational reformer. ^Mall 
appreciated more perhaps than most directors of scientific 
institutes the importance of the best material equipment for 
his laboratories, and made rigid rules to provide for its care 
and to prevent its deterioration. He trained technical assist- 
ants to relieve the scientific staff of much routine work. He 
believed that every laboratory director should be a good house- 
keeper, and the scrupulous cleanliness and jierfect order of 
his institute, marvelled at by all who had grown up under an 
older anatomical regime, reflected his opinion that the char- 
acter of the surroundings in which people work exerts a moral 
effect upon their conduct. Mall's organization of the Ana- 
tomical Laboratory of the medical school and later of the 
Embryological Institute of the Carnegie Institution was based 
upon a differentiation of function and a corresponding division 
of labor among the members of a staff. He knew how to dele- 
gate large responsibilities to subordinates, how to correlate 
the several activities of his department and how to maintain 
the oversight that is necessary to ensure the satisfactory 
progress of work. Indeed, he made his own the three watch- 
words of every successful executive, " Organize, Depute. 
Supervise." 

As a counsellor, Mali's advice was sought not only by those 
interested in anatomy but, and especially, by the leaders in 
this country of reforms in medical education. University presi- 
dents, heads of science departments, members of the directing 
boards of scientific institutes, and professional investigators 
of the evils of existing educational systems, conferred with 
him and were profoundly influenced by his opinion. In a 
number of articles that have been published since 1890 upon 
the improvement of the conditions in our medical schools and 
hospitals, the " insider " will have no difficulty in recognizing 
the tricklings from a well-known stream. He favored the 
foundation of whole-time clinical cliairs in our luedical 
schools and the writers who first urged this reform owed their 
seed-thoughts to stimulating discussions with him. In faculty 
meetings, and in large groups generally, Mall was retiring and 
for the most part silent. He was at his best tete-a-tete, for 
under four eyes, or in small groups, his taciturnity disappeared, 
and his speech to the sympathetic listener was free and always 
inspiring. His conversation was peculiarly stimulating to his 
friends on account of a certain cryptic character that depended 
on the frequent elision of associative links. His own mind 
worked so rapidly that it appeared to make leaps rather than 
to flow, and the interlocutor who was not agile enough to lea]) 



with him, or to intercalate for himself the materials necessary 
for continuity, would sometimes be at a loss to understand him. 
More than one man has been heard to say that he " could not 
make head nor tail of what Mall was saying." But to him 
who could and would follow, how rich was the reward ! Mall's 
example as an organizer, his wisdom as a counsellor, and his 
zeal as an educational reformer, have given the progressive 
movement in American science an impetus that will continue 
long after his death. 

A man absorbed in scientific pursuits does not always take 
time for the enjoyment of home and friends, or for the satis- 
faction of the sesthetic desires. But Mall was singularly happy 
in his home life and no one ever had stauncher friends or 
was more loyal in friendship than he. Married in 189.5, he 
found in his wife one who could sympathize fully with his 
work, who could share his ideals, who, with him, could disdain 
mere externals, and who felt it no sacrifice to give up many 
material and social pleasures when they conflicted with the 
interests of the higher intellectual life. To their home, per- 
sonal friends were always welcome, and on Sundays and holi- 
days members of the laboratory staff were frequently enter- 
tained there. Mall's personal solicitude for the welfare of 
members of his staff was touching. His suffering was acute 
when they were in trouble, and when successes came to them he 
was elated. He had no desire for, or satisfaction in, promis- 
cuity of social relationships, but wherever he was — at Clark 
University, at the University of Chicago, or in Baltimore — 
he drew to himself a small but congenial group of intimates, 
and to them he gave himself freely. Those thus advantaged 
were impressed with the fusion of sound sense with earnest 
enthusiasm that was characteristic of him. A little tinged 
with pessimism, he was, in reality, a meliorist, knowing that 
there is much to do (that can be done) to better man's estate. 
He had strong faith in the beneficent power of truth and of 
work. He believed in freedom of thought and he practiced 
freedom of speech. He was a striking example of a strong 
and a liberal spirit. Memory of him will continue to move 
the souls and to keep warm the hearts of those who knew and 
loved him. 

Dr. Simon Flexner. — The death of Doctor Mall is so recent 
and my grief for his loss so fresh that I find myself reflect- 
ing on the fruitful and delightful memories of our past 
association instead of writing out my impressions of his 
unusual persenality. 

Doctor Mall returned to Johns Hopkins in the late sumnici- 
of 1893, just before the medical school opened its doors 
to the first class of students in the autumn. It was then that 
we met. I recall vividly my excitement and nervousness when 
the rumor was circulated about the old pathological building 
that ]\Iall had arrived. His name had been a tradition among 
the small group in the pathological department. A few years 
earlier, before the hospital had been opened to patients, he 
had come to the laboratory and, as fellow in pathology, had 
performed a miracle of interesting and important studies on 
the connective tissue foundations of the organs. Fellows in 



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JOHNS HOPKINS HOSPITAL BULLETIN 



[Xo. 327 



pathology there had been since his time, but no one wuose 
memory was glorified as Mall's had been. We had so often 
heard him and his work spoken of by Doctor Welch, Doctor 
Halsted, and others, including the indispensable Schultz, who 
was for many years presiding genius over the technical and 
janitorial services of the laboratories and whose commendation 
carried with us such great weight, that I pictured ^lall as 
quite different from what in actual life he proved to be. 

One's fancy — my fancy surely was so — when young is apt to 
produce its own pictures. In my fanciful portrait of Mall I 
represented him as large, absorbed, and rather austere. Never 
was a fancy more completely and happily shattered. I can 
just remember our meeting; those who knew Mall well will 
never forget how engagingly he smiled. It was with one of 
the best of his smiles that he greeted me. 

That event was the auspicious beginning of a warm friend- 
ship which never wavered until his death. During the first 
period of half a dozen years we were in almost daily contact. 
Later, and after 1900, when I left the medical school to enter 
the University of Pennsylvania, our meetings were at first not 
infrequent. I shall never cease to regret the increasing inter- 
vals between them which followed my removal to the Rocke- 
feller Institute in New York. Increasing responsibilities and 
broadening duties play sad havoc with one's life, and I feel 
that I suffered a grievous and now irremediable loss m per- 
mitting those circumstances to cut me off to the extent it 
seemed inevitable they should from association with Mall. To 
a certain extent, letters took the place of personal contact. Thus 
I kept more or less in touch with the workings of his restless 
and constructive mind. 

It probably will strike few except his very intimate friends 
that Mall was by temperament a reformer. He was an uncom- 
promising democrat and hence entertained the firmest belief 
in liberty in its true and proper sense. Out of this intensity of 
conviction arose the views expressed in conversation more 
frequently but not more forcibly than in his addresses, on full 
opportunity and freedom in university education, both in its 
pregraduate and postgraduate aspects. His comprehending 
and incisive mind was the first, I believe, to appreciate and 
afterwards to propound that the best of medical educational 
institutions were half-hearted affairs. The part of the institu- 
tion which a quarter of a century earlier had been the weak- 
est — the laboratory branches namely — had been immeasurablv 
strengthened in that short period, during which the previously 
stronger part — namely the clinical branches — had progressed 
relatively little. The balance could be struck and must be, 
even though in the process the old system were, if need be, 
completely shattered, as much shattered indeed as had been the 
earlier hybrid combined laboratory and clinical chairs. Out 
of this conception which Mall propounded, I am almost in- 
clined to say preached to us persistently, arose the present 
movement ever gaining force and strength until it has now 
become almost irresistible, in favor of full time clinical 
professorships. 

It is very interesting to consider just here the extent to 
which he used others, converts or disciples as they may be 



called, to diffuse more broadly his reforming ideas. One would 
search Mall's miscellaneous papers, of which, indeed, there are 
notably few, in vain for an exhaustive presentation of the case 
for the full time clinical plan. The wide dissemination of the 
idea by the printed page was left to others, while he maintained 
the high level of conviction in those coming under his im- 
mediate influence by an irresistible fund of logical exposition. 

In his delightful essay on his master, Wilhelm His, Mall 
reveals his attitude toward higher education in its various 
complex aspects. I wonder how many returned foreign stu- 
dents have kept up an intimate correspondence with a revered 
teacher extending over a long period of time, like that dis- 
closed by Mall in this essay. The extracts from his let- 
ters there published show how well the older man compre- 
hended the younger, as the spirit and substance of the essay 
show how the younger man admired and appreciated the 
older. There is no doubt that His perceived in Mall rare 
personal and mental qualities, as he confides to him not only 
the subjects and trend of work, but his larger aspiration in the 
wide domain of anatomical research. In the light of the rela- 
tion there revealed one can surmise the satisfaction and joy 
with which His, had he lived, would have welcomed the estab- 
lishment of the Institute of Embryology with ilall as the first 
director. 

In my task of presenting a fragment of the personality of 
Mall as apparent to his intimate friends and associates, I find 
myself embarrassed by the many memories that crowd my 
mind. It is not easy to select episodes. I love, myself, to think 
of the period during which he lived, as did the medical officers, 
in The Johns Hopkins Hospital, for then we were almost con- 
stantly together. The small, older group of men — older, that 
is, than the internes — saw much of one another. Mall, Frank 
Smith, Thayer, Barker, and I met always at dinner, frequently 
at breakfast and luncheon at the small table at the head of 
the room. There was lively conversation and much variety 
of theme; and not a little good cheer. A small photographic 
print still exists which pictures the group; it is chiefly notable 
for the good likeness of Mall which it presents, showing iiiin 
as it does in one of his happiest moods. 

Mall returned to Baltimore as the first professor of anatomy 
of the new medical school. The physical conditions surround- 
ing the launching of the medical school were so simple as to 
be almost austere. Aside from the hospital — a model of com- 
pleteness at the time — the plan for housing the new depart- 
ments of the school we should now regard as meager in the 
extreme. I sometimes think that it may be well to recall from 
time to time the simple beginnings out of which the great 
institution of The Johns Hopkins Medical School arose. The 
only additions made to the hospital buildings, to accommodate 
the departments of anatomy and physiological chemistry and 
pharmacology, were twQ stories added to the original small 
pathological building erected as a mortuary for the hospital 
and already housing the entire pathological department. It 
was in the upper, or fourth story of that enlarged building that 
the complex department of anatomy took origin. 



May, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



115 



Some one else, who traces the growth of anatomy at the 
medical school, can tell better than I can how Mall adapted 
the limited space and facilities at his command to the teachina- 
of anatomy, histology, and embryology, and to the conduct of 
research. There was no actual break in the continuity of his 
own investigations, and very soon after the medical classes 
were taken in he began to produce the new work which in a 
steady and increasing stream has come out of the anatomical 
department. 

There were not a few obstacles to be overcome in getting the 
student's work properly started. I recall the shifts he was 
obliged to make to bridge over the gaps in dissecting until 
human cadavers became available. This period was for Mall. 
in many ways, an anxious one. But it was not long before thi< 
particular obstacle was overcome, and because of the improve- 
ments which he introduced in the preservation of human 
cadavers, his laboratory .soon became the custodian of all the 
anatomical material employed for dissection and surgical in- 
struction throughout the city. 

The kind of teaching which Mall gave to his students has 
been described ; there was no lecturing in his curriculum. He 
had almost a horror of lectures in anatomy ; the idea collided 
with his fundamental conception of how so practical a sub- 
ject is to be acquired. In his views there was one road 
only to that goal. The student must teach himself in order 
to learn. Hence there were provided the objects to be dis- 
sected, text-books, atlases, models, and time, with a sufficiency 
but no excess of instructors or guides. He saw no virtue in 
exhibiting and describing a predissected part, provided the 
students were given opportunity to dissect for themselves. 
That this principle is sound no one will, I think, now deny. 
That its operation has produced a remarkably large number of 
superior, independent, and broad anatomists, the liistory of 
his department amply shows. 

But a confusion of method and man is often made with 
disastrous consequences. It is easy to imagine this mode of 
teaching anatomy adopted widely without yielding the results 
which JIall obtained. To put the method into effect would 
doubtless represent a great advance over the old system, but 
without a strong, able teacher and guide, such as Mall was, the 
phenomenal results which he achieved would not be attained. 
In other words, he was a sound innovator because he was a 
.strong man. He was a successful leader in anatomy because 
he was learned and original. He has left a rich heritage to 
science through his own labors and those of his pupils, because 
to all his other qualities he added the rare ones of wisdom, 
kindness, and generosity. 

Our proximity in the pathological building brought us into 
frequent association. In the early days of the medical school. 
Mall often attended the autopsies, many of which I performed. 
His active interest in the pathological phenomena continued 
throughout his life, in part possibly as the result of the year 
spent as fellow in pathology under Doctor Welch. But in 
fact he did not dissociate, as is often erroneously done, facts 
of pathology from those of anatomy. Being naturally inquisi- 
tive in regard to the relation of cause and effect in respect to 



the unit forms of organs, he was also prone to inquire into 
the effects of causes in their nature pathological. 

At about the period when Mall was studying the lobular 
unit of the liver I was induced to attempt the application of 
some of the methods he worked out to cirrhosis of that organ — 
a mere illustration of the way in which two related dei:)artments 
through him were made to react on each other. 

I imagine that few who knew Mall even quite well realize 
with what intensity of absorption and application he would 
work at a problem once he had gripped it, as one might say. In 
temperament he was naturally reflective. Hence there oc- 
curred periods during which he appeared to be doing little in 
his laboratory. At such times he would become possessed with 
the impulse to roam about the building or out into the city 
or into the adjacent country. It was remarkable that when 
under the influence of those moods he did not seek solitude so 
much as another form of activity. I was not infrequently 
taken away by him for a stroll through East Baltimore, and 
on these expeditions I acquired quite a knowledge of that part 
of the city. They were in many ways extremely interesting 
occasions, for during them he often talked his best and sketched 
advanced ideas on educational and other reforms, as well as 
on problems of research. I think j\Iall never dreamt idly. 
He was possessed of a romantic imagination, but it was both 
controlled and constructive. To not a few who did not under- 
stand him well his ideas sometimes sounded extreme, but they 
invariably rested on real foundations, as is now evident since 
so many of them have been carried into practical affairs. 

At other times he worked out problems in his laboratorv' 
with consuming intensity. It would seem as if while under 
what I have called the spell of his reflective mood, a problem 
would formulate itself more definitely, or some barring obstacle 
give way to a revealed point of view. ' However that may be, 
my notion was that the periods of reflection were signs that 
he would attack a new or solve an old problem ; and I always 
looked for new ideas and accomplishments when the mood 
changed. 

If I have at all succeeded in revealing Doctor ilall as lie 
appeared to me, then I have presented to you a complex per- 
sonality. The remarkable thing is the way in which all the 
pronounced qualities that characterized him were fused into 
a simple, harmonious, kind and lovable individuality. I have 
referred already to Mall's democratic spirit. He was an in- 
tense lover and active exponent of liberty. His belief and 
confidence in freedom extended far beyond the confines of the 
university and laboratory, and into the world of politics and 
government. Freedom within the university he held as the 
first condition of the successful struggle of the forces of light 
over superstition and darkness. Within the walls of his 
laboratory the fullest liberty prevailed. Once outside the 
realm of the prescribed task for training, each man followed 
the bent of his own talents and tastes. However, his principles 
as well as his practice sharply differentiated between liberty 
and license: hence the rise under him of a group of strong, 
independent, but .sound teachers and investigators. Mall would 
probably have combated the suggestion that he produced a 



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JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 327 



school of anatomists, using the term in its usual significance. 
He would probably have insisted that he merely continued in 
America the .system which he pursued or saw in force in 
Switzerland and Germany. But I believe rather that he made 
such definite contributions to the higher education and train- 
ing of anatomists, and produced in, alas ! a few brief years so 
large a number of varied and capable teachers and investiga- 
tors, as to mark a new era in the history of higher educational 
endeavor. 

1 .said that his deep convictions on freedom carried him into 
the wider domain of social liberty. Mall never propagandized 
on this subject. Nevertheless, he felt intensely about it. It 
is noteworthy that with all the admiration for the freedom 
of migration from university to university and the wide elec- 
tion of subjects and ideas in the German university, to the 
social and political conditions of that country he was anti- 
pathetic. To so strong a " democrat," to use that term in its 
wider and better significance, a studied paternalism and im- 
perialistic tendency were deeply unsympathetic. 

Mall's sincerity, self-eifacement, and never failing considera- 
tion were at the root of his noble qualities and made com- 
panionship with him a rare privilege. I have already spoken 
of my own good fortune in possessing in some degree his inti- 
mate friendship. It is a rare possession, indeed, and one to be 
cherished. But I owe him also an educational impress, none 
the less valuable becau.se of its subtle nature. I am of the 
opinion that his pupils were influenced by this unusual quality 
which because of its elusiveness seems an emanation — so little 
was it given olf or received with innnediate conscious 
perception. 

Mall was absorbed in ideas. They formed the substance nl' 
his serious talk, but he was by no means a stranger to the 
lighter side of human relations, for he possessed a gentle and 
engaging humor which might even, when provoked, become 
a little biting. It took time and skill to penetrate an outer 
film of reserve which arose from innate modesty and shyness, 
iiut once beneatli that protective covering, one readily dis- 
covered in him a simple, idealistic, and gifted person of many 
sides, possessed of an almost miraculous power to stimulate 
students to put forth their best efforts. His memory and 
example will long survive in the achievements of his students 
and associates, in the broad ideas which lie disseminated, and 
in the admiration and affection which he iiispircil. 

Dr. Florence Rena Sabin. — To those who are familiar with 
the history of medicine in this country it is a matter of 
common knowledge that at the time Dr. Mall began his career, 
150 years ago, anatomy in America had no scientific stand- 
ing, a mere tool of surgery, with but a single method, that of 
dissection. He left it where it must be, and always has been 
in any community where medicine is progressive — one of its 
great sciences. He has left it richly endowed with technical 
methods, a .science so truly fundamental that the workers in 
every other branch of medicine are constantly and increasinglv 
returning to it, both for methods and results. TJie vision of 
this change must have been his while he was yet a student for 
he wrote in one of his letters: " iMv aim is to make scientific 



medicine a life work. If opportunities present I will. This 
has been my plan ever since I left America and not until of 
late (since having received encouragement) have I expressed 
myself. I shall no doubt meet many stumbling blocks, but they 
are anticipated." 

Sweeping aside the traditions of the dissecting room, he first 
created conditions under which this change could develop, and 
then devoted himself to scientific achievement, and to the 
type of teaching in which he was profoundly interested. It 
was one of his oft repeated maxim.s, that the best, and perhaps 
the only great way to teach, is by example. With the ideal 
of scientific work as his goal he has left us an example .so rich 
in ideas, so varied in technical methods and so representative 
of the range of anatomy and embryology, that a study of his 
work is both an inspiration and an education. 

His ver\' first undertaking in the field of research serves well 
to illustrate his independence of thought which to those who 
knew him was one of his most striking characteristics. During 
the winter of 1885 he began his scientific work under His at 
Leipzig, who gave to him the study of the gill-arches in the 
chick. Four years prior to that time His had studied the same 
region in a human embryo. He noted that the gill-arches do 
not break through into the pharynx, but that a depression of 
the ectoderm develops over the region of the third and fourth 
arches, and concluded that the thymus must arise from the 
ectoderm of this depression. Dr. Mall evidently made his 
study independently, cut his own series, made reconstructions 
and came to the conclusion, now generally accepted, that the 
thymus arises, not from ectoderm, but from the endoderm 
lining the pharynx. At the end of the winters work he pre- 
sented his results to His in the form of a finished manuscript 
in English. His could not, however, accept this conclusion so 
directly opposed to his own view and asked his pupil to restudy 
the subject. This he did the following winter while in Lud- 
wig's laboratory, translating his manuscript into German. 
The work was given to His a second time and accepted for 
]jublication, just as Dr. Mall was leaving for Baltimore. In 
the next number of the journal of which His was editor, there 
a]ipeared a second conununication from the latter, strengthen- 
ing his own ])oint of view, but announcing that a different 
(i|iiniiin wonlil lie pul)lished by one of his pupils in the next 
nnmbcr. W hen Dr. ^Fall's article appeared it was with a 
damaging footnote by His, to the cflTect that the independent 
character of the results was obvious. During his early months 
in Baltimore, Dr. Mall established his jioint in a mammiiliaii 
enil)rvo, and two years later His restudicd the region in a 
human enibryu and found that Dr._ Mall's conclusions were 
(■(irrccf. lie gave (hic acknowledgment in an open leftci- to 
l>i-. Mall ]uiblisbed in the same journal in which lie states 
frankly. "Sic haben gegen mich TJecht."" ' This letter ce- 
mented a life-long friendship, as can readily be seen from the 
correspondence accompanying Dr. Mall's article, " An estimate 
of the work of His."' 



' His, W. : Sclilundspalten und Tliymusanlage. Aus einem Briefe 
von W. His an F. Mall in Baltimore. Arch. f. Anat. u. Phys., Anat. 
Abth., 1S89. 



May, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



117 



During the winter of 1885, His suggested that Dr. Mall 
work under the great physiologist, Ludwig. As Ludwig's 
laboratory was always full, the opportunity was slow in com- 
ing; indeed, as Dr. Mall wrote home, he was leaving Leipzig 
with no hope; his trunk was even on the way to the station 
when the letter came that the opportunity he so much desired 
was his. So great was the influence of Ludwig over his mind, 
character and future work that it is impossible to overestimate 
it. He himself summed it up in these words, " To that master 
I owe much — all." Ludwig assigned him the study of the villus 
of the intestine. As he stated in one of his letters almost his 
first impression was that here was a subject which had occupied 
the minds of the greatest anatomists of the past century. 
Repeatedly throughout Dr. Mall's writings there is to be found 
that expression of regard for the work of great minds. Widely 
read in his own subject, it was of the works which have lived 
and will live that he made a profound study. 

Jn Ludwig's laboratory Dr. Mall learned the methods of 
injecting blood-vessels and lymphatics, and his studies of the 
vascular system of the intestine and stomach are familiar to 
every student of medicine. Under the influence of Ludwig, his 
work was characterized by a very strong physiological bent. 
Indeed, it may be said that his work was physiology in the 
hands of one with an intense interest in structure. In the 
work on the intestine, and more clearly still in that on the 
stomach, he was absorbed in the mechanism of all the jjarts of 
the organ. 

In some of the foreign universities it was the custom for a 
new incumbent of a chair to deliver an address giving, as it 
were, a " prophecy " or a " program " of his future work. Such 
a program was the famous address of His on accepting a chair 
in the Swiss University of Basel. In some such way the article 
of Mall on the stomach, published in the first volume of The 
Johns Hopkins Hospital Eeports, gave his program of the 
way in which he proposed to study anatomy. This paper lays 
a foundation for what may be called physiological aitatomi/ 
and in it can be traced the beginnings of many of Dr. Mall's 
ideas. He studied the stomach from every aspect and with 
a wide range of methods. There were experiments m diges- 
tion bringing evidence to support the view that the acid is 
secreted only in the region of the fundus ; here is the beginning 
of his brilliant studies on connective tissue, in which he be- 
came interested through noting the arrangement of the fibers 
of the submucosa. Here also are observations on smooth muscle 
which led to the study of the types of contraction-waves in the 
intestine, and later to experiments on the reversal of these 
waves. In his paper on the stomach is this brief note : " Re- 
cently I have found that irritation of the splanelmic nerve 
causes contraction of the mesenteric vein." He probably first 
made this observation in Ludwig's laboratory, and subsequently 
proved that the portal vein is supplied with vaso-motor nerves, 
one of the valuable discoveries in physiology. 

The most important idea of his early work from the stand- 
point of anatomy, was that of structural units, which Dr. Mall 
conceived from the study of the villus. He noted that the 
villus was the unit of function of the intestine, and this theorv 



of structural units can be followed through a long series of 
investigations, in part by himself and in part by his pupils. 
In fact almost every organ of the body has now been studied 
from this point of view, and almost every organ except the 
nervous system can be simplified by this conception. The 
theory reaches its best expression in Dr. Mall's own articles 
on the liver and spleen, in which he states that organs are 
made up of ultimate histological units represented in the 
vascular system by the capillary bed which intervenes between 
a terminal artery and its corresponding vein. At this point the 
two cease to accompany each other and are separated by the 
maximal distance, that is the length of the capillaries. Thus 
the length of the capillary determines the size of the unit. 
These ultimate histological units are grouped together into 
lobules which vary considerably in the different organs of 
the body. They are not only of great structural significance, 
since an organ is to be considered as a multiplication of them, 
but are also of significance to physiology, since such units are 
equal in function. For example, a unit of a gland gives a unit 
of secretion. This equality in size and function comes from 
the laws of growth of an organ : when a unit increases in size, 
so that the length of its capillaries increases beyond the norm, 
a new artery develops, the single unit splitting into two. Thus, 
from the general theory of structural units. Dr. Mall was led 
into one of the aspects of the problem of growth ; namely, how 
a small organ becomes a large one. This problem he often 
discussed in the laboratory. In his article on the liver he gives 
the clearest expression of it. There he develops the theory of 
Telle and Sabourin that the portal unit, not the hepatic lobule. 
is the real unit of structure and function, since the portal units 
are equal in size and are also the centers of growth in the liver. 
During growth these units are constantly fractured and de- 
stroyed as new units develop, and it is this interstitial growth 
in organs which makes the .subject so difficult to follow. 

In his study on the spleen Dr. Mall brings out best the rela- 
tion of all the tissues of an organ to its function. Thus the 
spleen is an organ based upon the vascular system; its histo- 
logical units are grouped into lobules which are outlined in- 
dense bands of connective tissue. The arteries in the.se lobules 
end in swellings — the ampulla of Thoma — where the endo- 
thelium changes from the typical complete lining of a blood- 
vessel and becomes a reticulum with open meshes. This change 
in the endothelium, demonstrated histologically by ilollier in 
1911, had been fully described by Dr. ilall 11 years earlier. 
Through these openings in the ampulla; both the blood-])lasma 
and the corpuscles pass freely into the pulp and thence back 
into the rich plexes of veins which fill the lobule through cor- 
responding holes in their walls. By experiments Dr. Mall 
showed that the emptying of the pulp-spaces into this plexus 
of sinusoidal veins is accomplished by means of the contraction 
of the bands of smooth muscle in the trabecuk\ As the.se 
l)ands contract, the trabecule of reticulum upon which they 
run tend to pull open the interlobular veins, while at the same 
time they compress the arteries. Thus the splenic pulp, one 
of the most difficult enigmas in histology, is seen to serve as the 
capillary bed of the spleen. This study of structural units 



118 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 327 



grew out of the work in Ludwig's laboratory, and may be con- 
sidered as the foundation for a new phase of anatomy, a step 
beyond morphology, i. e., the study of the adaptation of the 
minute structure of organs to their function. 

More than any other anatomist, Dr. Mall has also enricheil 
our knowledge of the fibers of the connective tissue. He ana- 
lyzed the differences between elastic fibers, white fibers and a 
modification of the latter — the reticulum, which fonns the 
framework of organs. In this study he used the methods of 
bacteriology and of chemistr}% adapting them to his needs and 
producing the most beautiful specimens of reticulum to be 
found in anatomical literature. This study he illuminated In- 
showing that the framework of organs is not an inert structure. 
but is adapted to the function of each organ. His account of 
the origin of the fibers of connective tissue from cells, though 
recently called into question, will, I believe, hold. 

One of his valuable contributions is the study of the structure 
of the heart. He grasped the significance of the work of Krchl, 
which he said bore the stamp of Ludwig. Krehl demonstrated 
that when a heart is macerated in a weak acid, the atria can 
be lifted from the ventricles, thus exposing the atrio-ventricular 
rings, which are of fundamental importance for a proper un- 
derstanding of the structure and function of the heart. In 
other words they are the tendons of origin of the bands of 
heart-muscle. Dr. Mall saw that this discovery reopened the 
subject of the architecture of the heart; and that here was a 
point where progress could be made. In 1900 he gave to John 
Bruce MacCallum the study of the bands of the heart-muscle. 
MacCallum unraveled the ventricles of the heart in the embryo 
pig into superficial and deep spiral bands with their origin 
and insertion in two tendons, the atrio-ventricular rings and 
the chordae tendineae. As a tribute to this brilliant work, Dr. 
Mall completed the study on the adult human heart after 
MacCallum's death, reducing the problem to the following- 
simple terms : To understand the beat of the heart one must 
figure out how a nniscular bag is constructed so as to empty 
itself. We have Dr. Mall's specimens in the laboratory show- 
ing how the spiral cardiac bands contract with each beat of the 
heart in the exact familiar pattern of wringing out a rag. This 
prompted Dr. Mall to reconsider the development of the heart, 
and his work here led to what he considered the next step, 
that of following out the origin and development of the atrio- 
ventricular bundle and the Purkinjc bands. 

Another line of anatomical study which interested him was 
the study of the brain. Here he has drawn to the anthropo- 
logical side. He realized that Baltimore afforded a rare oppor- 
tunity to study the problem of race in connection with the 
brain. Dr. Hrdlicka, the anthropologist in Washington, had 
said to him that the brain of a negro could be distingnislied 
from that of a white man, and with this in mind Dr. Mall 
made a comparative study of the brains in the anatomical col- 
lection, comparing them by weights, the complexity of their 
convolutions, the area of the cross-section of the frontal part 
of the corpus callosum, and other criteria. Idealizing that no 
man can free himself of prejudice, he charted all of his data 
by means of numbers, filling in the race and sex only after the 



charts were complete. In this way he showed that the crude 
present day methods are inadequate for scientific deductions 
regarding the relation of the brain to race and sex. Of the 
criteria on race there remains only the difference in the shape 
of the brain corresponding to the well-known difference in the 
shape of the head. He was profoundly interested in the subject 
of the development of the brain. After the monograph of 
His on the development of the tracts in the brain written 
during his last year, Dr. Mall plotted out such tracts as could 
be made out in the brains of his specimens, and it was, I know, 
one of his great desires to see this problem developed in the 
new Carnegie Laboratory of Embryologj'. 

In his anatomical studies Dr. Mall has enriched his science 
with a wide range of methods. Our laboratory is full of 
examples of beautiful injections, corrosions of blood-vessels, 
preparations of connective tissue made by differential digestion 
and maceration, cleared embryos which show the development 
of the skeleton, and many others. Through his influence the 
technique of modelling has been greatly improved and ex- 
tended. His own methods of work in the laboratory are of 
great interest, and he frequently discussed the influence of 
Ludwig in this connection. Contrary to the usual type. Dr. 
Mall was far more active mentally than physically. I have 
known him to think and plan with the greatest care so that a 
bit of routine might be simplified. Thus, it was his habit to 
think out every detail of an experiment before he undertook it : 
he never employed the system of trying a thing out without 
adequate preparation, or of approximating his methods through 
errors. For this reason he made but one experiment a day. 
If he failed he would not repeat it until the next day, thus 
giving himself ample time to think out the reasons of his 
failure. 

He was very intolerant of the collection of unanalyzed ma- 
terial. His interest in technical procedures was only in their 
bearing upon the solving of problems ; it lay in understanding 
the principles rather than in multiplying evidence. 

We have outlined Dr. flail's work in anatomy as it grew out 
of his work in Ludwig's laboratory, and we shall sum it up l)y 
saying that he approached anatomy with an interest in struc- 
ture as adapted to function rather than in morphology. But 
he was not only an anatomist, he was also an embryologist. 
In 1891, he published an account of a normal human embryo, 
now placed in the fourth week of development. He made a 
most careful and accurate study of all its systems, illustrated 
by the surface form, in models and casts. This was the first 
human embrj'o ever modeled in America, and at that time it 
was the most complete account of any human embryo in 
existence. In this study he announced several discoveries. 
He described a new stage in the development of the brain and 
its nerves, and traced the origin of the splanchnic nerves. Here 
also was repeated one of Dr. Mall's earlier discoveries, namely 
that the Eustachian tube and middle ear arise from the first 
branchial arch, and in this study lay the foundation of his 
studies on the crelom and the vasciilar system. The effect of 
this work on Dr. JIall is to be seen in these words in one of his 
publications: "I always think in human anatomy in relation 



May, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



119 



to this embryo." Huber has said that this study has served as a 
model for all future work of its type. It did more, for like his 
work on the stomach, it represents, as it were. Dr. Mall's pro- 
gram in embryology. Here one can see the beginning of the 
type of embryological work which will be associated with his 
name. 

This specimen forms the foundation of the priceless col- 
lection of over two thousand human embryos which Dr. Mall 
later gave to the Department of Embryology of the Carnegie 
Institution of Washington. It was perfect, beautifully fixed 
and sectioned. When he had finished the description of it he 
offered it as a tribute to his teacher. His. His returned it, 
with several others of his own, expressing the wish that they 
might be the nucleus for a much larger collection. How richly 
has this gift borne fruit in the development of the science of 
embryology ! 

In the study of embrj^onic development three names stand 
out in logical sequence, von Baer, His, Mall. Neither His 
nor Dr. Mall were concerned with the phenomena of matura- 
tion, fertilization or the cleavage stages, in the develop- 
ment of the embryo, but the latter has characterized the work 
of His as laying a foundation for histogenesis. In like manner 
the work of Dr. Mall in normal embryology may be summed up 
in the term organogenesis. He has traced the growth of 
organs up to their adult stage. He has laid the foundation for 
a complete anatomical survey of the human embryo in all stages 
of its development. Here, for example, belong his studies 
on the diaphragm. Based on the discovery of His that the 
diaphragm arises in the head, in the septum transversum, 
and shifts caudalward. Dr. Mall determined the origin of the 
pleuro-pericardial membranes and the pillars of the dia- 
phragm, and then traced the shifting of the diaphragm to 
its final position in the adult. The same type of work is seen 
in the study of the ventral abdominal walls, following the 
shifting of the rectus muscle, and still more clearly is it 
brought out in his study of the loops of the intestine. He 
followed the pattern and position of these loops, first in their 
early shifting from the coelom into the cord, and subse- 
quently studied the mechanism of their return back into the 
abdominal cavity as the foetus develops. In the dissecting 
room he determined the normal position of the loops in the 
adult, and by experiments on animals showed that both the 
intestine and the omentum seek their normal poi^ition when 
disturbed. Of this work His wrote : 

Your satisfaction in your work will be lasting, because you have 
brought light into a field which was so obscure. The thing which 
has been lacking in all of our studies on development up to this 
time has been observations on the transition between the early 
embryonic and foetal stages up to the form of the adult. For the 
intestine you have given the entire study from the beginning up 
to the end, and I regard it a great step in advance. 

It is in connection with the development of the vascular 
system that Dr. Mall made some of his most significant con- 
tributions to embryology. One of the most important points 
in the study of the embryo mentioned above was solving the 
problem of the primitive ventral branches of the aorta. This 
he did by showing that the vessels which are the forerunners 



of the cceliac axis and superior mesenteric artery arise as far 
forward as the first dorsal segment, and by indicating the 
method by which they shift back to their position in the adult. 
This work has since been repeated with more specimens but 
not analyzed with more insight. I recall in connection with 
these more elaborate subsequent studies on this subject one 
of Dr. Mall's characteristic comments : " I can never become 
interested in the mere collection of new examples after a prin- 
ciple has once been thoroughly established." It is in his work 
on the development of the vascular system that his physio- 
logical bent and the theories he entertained concerning growth 
gradually converge. He saw the fundamental significance 
of endothelium in connection with the vascular system; that 
blood vessels are not parts of the great system of tissue-spaces, 
with their slow movement of the fluid contained, but are 
determined rather by a special smooth lining of a differen- 
tiated cell or endothelium. He carried over to embrj-ology 
the methods of injection of blood-vessels and lymphatics in 
use for the adult and thereby made possible the study of the 
spread of vessels in the embryo of his own work and that of 
his students, as illustrated in the Manual of Human EmJiry- 
ology, edited by Keibel and Mall. There is represented the 
progress which was made by the laboratory under his guidance. 
He established the method by which it will be possible to give 
a complete account of the development of the vascular system. 

Dr. Mall also discovered the fact, now abundantly confirmed, 
that endothelium ran give rise to the fibers of reticulum. 
In the study of the vascular system he emphasized again and 
again the value of the study of the organ as a whole. Trained 
by the man who invented the microtome and himself making 
improvements on it, he reacted strongly against those anato- 
nii!5ts who study only sections. He was interested in the archi- 
tecture of an organ; to use one of his own phrases he had 
" a feeling for a structure." Indeed he has often said that if 
he were to choose a career again, it would be that of an archi- 
tect. His gift in anatomy, like the gift of a sculptor or the 
architect, was the power to visualize structure in three dimen- 
sions. Thus one can understand his pleasure in the studies of 
the architecture of the vessels of organs, given not in indefinite 
terms but showing the exact pattern of all the vessels, the 
number and relation, the order of arteries from the main to 
the terminal branches. Thus he has left to us a rich heritage 
of corrosions of all of the arteries and veins of various organs 
which is worthy of a place in the great scientific museums of 
the world. In the study of the development of the vascular 
system he, more than any one else, has analyzed the laws of 
vascular growth as outlined by Thoma. 

During the latter part of his life. Dr. ilall became more 
and more interested in the problems associated with his col- 
lection ; that is to say, in the type of problems for which 
institutes for research are founded, and which depend for 
their solution upon the analysis of a large amount of material 
and the cooperation of experts along closely allied lines. These 
problems touch more and more closely the problems of clinical 
medicine and social welfare. Such, for example, is the study 
of abnormal embryos, leading up to the analysis of their fre- 



120 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 32: 



queucy and causes, the study of tubal pregnancy, the normal 
curve of growth for the human embryo, the determination nl' 
its age, the nature of implantation, and the causes of sterility 
and abortion. He first became interested in the study ot 
abnormal embryos through separating the normal from the 
abnormal in his collection. In 1893 he described a specimen. 
then the youngest in his collection, as a normal embryo of 
the second week, and later concluded that it was an older 
abnormal embrj-o. His first general account of abnormal 
embryos was in the volume of The Johns Hopkins Hospital 
Reports, published in honor of Dr. Welch in 1900. Eight 
years later he published a monograph on monsters of which 
Morgan wrote : 

The recent publication by Mall on the causes underlying the 
origin of human monsters marks an epoch in the study of tera- 
tology in this country, tor he has treated the subject with a 
breadth of view and a wealth of illustrations rarely found in the 
handling of this complex question. Mall has brought to the task 
a profound knowledge of the older literature of the subject, an 
appreciation of the most modern results in e.xperimental tera- 
tology, and a thorough familiarity at first hand with the subject 
of human monsters. The physician and anatomist are brought 
into close touch with the work generally supposed to be outside 
their proper field; and on the other hand the student of malfor- 
mations in the lower animals will be made to appreciate the inex- 
haustible supply of human materials with which the anatomist 
and physician are familiar. 

In tliis study and in the work of the last six years, i.)r. ilall 
has given a masterly analysis of the causes of monsters. He 
has shown that from the earliest ages of the world's history 
the study of monsters has been one of the capital problems of 
anatomy, medicine and natural history; that the bolieC in 
supernatural causes gave way to the theory of maternal im- 
pressions, and that this must now give way to a seientilie 
analysis of their causes. Dr. Mall recognized that a few 
abnormalities, Polydactyly for example, are germinal and can- 
not be produced experimentally ; but that monsters are nut 
due to germinal or hereditary causes, but are produced from 
normal embryos by influences which are to be sought in their 
environment. The cause of monsters, he has indicated, lies 
buried in the non-committal term of faulty implaiilalinn. 
Thus the study of normal and abnormal implantation of the 
embryo became one of the chief problems which he proposed 
to study in the new institute of embryology. In his recent 
paper on cyclopia he has given a masterly analysis of the recent 
work in experimental embryology. He showed that as soon as 
Stockard succeeded in experimenting with eggs in suc:h a way 
as to produce cyclopean monsters at will, the explanation of 
the process was at hand; for the work demonstrated that a 
slight change in chemical environment, acting at a critical 
time, caused cyclopia. Hr. Mall studied the cyclopean mmi- 
sters in his collection, one uf which is at a stage where a com- 
plete analysis could be made, and in conclusion he says: " It 
seems to me that the studies based upon our collection of 
embryos, as well as recent investigations in experimental 
embryology set at rest for all time the question of the causa- 
tion of monsters. It lias lieen my aim to demonstrate that tlu' 
embryos found in pathological human ova and those olitained 



experimentally in animals are not analogous or similar, but 
identical. A double monster or a cyclopean fish is iden- 
tical with the same condition in human beings. In all cases 
monsters are produced by external causes acting upon 
the ovum." Thus, most localized abnormalities and monsters, 
of which he gives a wealth of illustrations, can be traced back 
to the faulty nutrition of the embryo at early critical stages, 
and the effects can be followed with every grade of intensity, 
from complete degeneration of the ovum to monsters which 
survive to term. One of his most interesting deductions is 
that in some forms of faulty implantation there results 
dissociation of the tissues of the embrv'O, so that they grow- 
exactly as do the cells in experiments with tissue-culture, with- 
out the correlating forces which check and integrate the organs 
in normal develojiment. 

It is to my mind a significant example that this work was 
carried on during the years given to the organization of a 
new department, that the work of administration was so 
planned that it did not check research. It is not too much to 
say that this work of Dr. Mall opens up a whole new field, 
and that it has already formed a broad foundation on which 
all future study of abnormalities in development must rest. 
Such was the work with which he was engaged at the time of 
his death. In his vision of an institute for embryological 
research he saw that two great lines of work in which he was 
most interested could be brought to a sticcessful conclusion 
within a reasonable limit of time. First, that the full develoji- 
ment of the study of organogenesis could give us a completely 
rationalized anatomy, and that only by completing the story 
of the development of the organism could we hope to under- 
stand its normal structure and its range of variation. Second, 
that there is a group of problems such as determination of 
the curve of growth, the study of abnormalities and their 
causes, normal and abnormal implantation and others which 
may be grouped together under the study of the laws of growth 
which lie beyond the ])owers of a single individual, and are thus 
only to be attacked through organized research. How often 
has he said during the latter months of his life, "my work 
is mapped out for the next ten years." FortniiMtely in his 
"plea for an institute of human emliryology." and in sdiiie 
unpublished manuscripts some of these ]ilans ai'e n'eunled. 
but for the loss of those coming years that wnuld have given 
us his greatest achievements, those achievements for which his 
whole life has been the preparation, no philosojihy can console 
us. About a month before his death he put the question to 
me : " What would you say had been the effect of the Carnegie 
Institute of Embryology upon this laboratory?" to which 1 
replied : " It has lifted the research of the place from a some- 
what amateurish state to a professional state." \ever shall 
I forget the jileasure in his face as he replied, " it is exactly 
what I wished to do." Such was his aim, such the ideal from 
which he had never swerved from the very lieginning of his 
career. 

No account of Dr. JlalTs seientilie woi-k is cdinplete without 
a mention of his contribnlion in the training of others. It is 
well known tha,t Ludwig published but little under his own 



May, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



121 



name, so that as time goes on most of his ideas will live throush 
the works of those he trained. Dr. Mall has done both ; wliat 
lie himself accomplished has just been only briefly recorded 
from a study of something over a hundred works from hi- 
pen. Besides this he has developed in this country what might 
be termed a school of anatomy, represented by five hundred 
articles which have appeared from his laboratory. Of teaching 
he had the highest ideal. He once said, " What higher title 
could there be than that of a great teacher?" That he him- 
self was one of the world's great teachers will be realized when 
his influence in the development of medical education in this 
country is adequately analyzed. To the general problems of 
education he gave deep thought and great originality. His 
teaching was characterized by two broad principles, which 
were followed in his own laboratory: First, that each student 
should approach his work in the spirit of a discoverer. Second, 
that since in each class there may be those who are destined 
to become the intellectual leaders of the next generation, liberty 
in education is absolutely essential, in order that the strong 
personality might develop. His own methods of training 
others were unique — so bound up with his own rare personality 
that none could copy, and few describe them. He had a gift. 
perhaps a genius, for stimulating thought. Rarely, indeed, 
by question; the quiz he never used ; it was more in the nature 
•of an occasional suggestion, the acuteness of which impressed 
one more and more profoundly as one pondered over it. Per- 
haps his most fundamental quality was his rare generosity 
which, I am convinced, he would freely ascribe to the influence 
of Ludwig. I recall distinctly an instance in which a student 
had worked carefully and accurately with him without, how- 
ever, understanding the meaning of the value of his observa- 
tions. The student became discouraged and had decided t<i 
give up the work, when Dr. ilall asked for his notes, and later 
published a very interesting paper under the student's name. 
This incident is most interesting in connection with one of 
Dr. Mall's letters, written in the early days of the medical 
school when he was homesick for the laboratory of Leipzig. 
He cites therein that before leaving Leipzig he had given some 
incomplete studies to Ludwig evidently expecting him to use 
them in his own work, but that Ludwig had added experiments 
and published them all under Dr. Mall's name. He then con- 
<'ludes : '' Can you blame anyone for wanting to return to one 
who would do things like that?" Ludwig, he wrote, was 
entirely without selfishness, and when I tried to thank him 
for all he had done Ludwig replied, " Pass it on.'" This, 
indeed, became the great watchword of Dr. MalTs life. Most 
freely did he give his ideas and his energies to his students. 
You will find no joint research with his students because all 
that he gave them he meant to be theirs. He demanded in 
return the development of high standards of work. In fact, 
perhaps the most lasting efl'ect which he made upon the minds 
of his followers was the value of scientific standards and the 
meaning of ideals in research. He never gave first hand 
praise ; the only encouragement which a pupil received was a 
genuine interest in his work, but what a rare enjoyment when 
the teacher discussed with the student his prejjaration. Hi' 



made the rounds of the laboratory nearly every day and gave 
his staff and his students much of his time. Each one learned 
that Dr. Mall was sure to come while he was making progress 
to enjoy it with him, and thus the student came to find enjoy- 
ment where Dr. Mall found his — in the work itself, ilany 
of his informal talks in the laboratory were on general topics 
rather than on the specific development of research, and so 
general, often so whimsical were these discussions that their 
meaning was lost entirely upon more than one student. 

In the organization of departments there are leaders who 
train others only in their own problems, giving little scope 
for independent work. Dr. Mall, on the contrary, was keen 
to give opportunities to those who could develop an indepen- 
dent line of research. Thus, for example, in his laboratory 
developed the method of tissue-culture. Again, though his 
own work did not lead him into the newer fields of cytology, 
he saw to it that this work was represented in the laboratory. 
An even more striking example, perhaps, is that he was the 
first to see that the methods of anthropology might be applied 
with great value to the study of embryology, hence he brought 
into the department of embryology professional anthro- 
pologists, thereby widening the scope of the science of em- 
bryology. 

Closely bound up with his own scientific achievements is the 
part he played in the development of scientific publications 
in this country. According to his own account, when he started 
out he hoped that the excellent Journal of Morphology would 
care for all the more complete publications of the laboratory, 
but it became hampered financially and finally suspended 
publication in 1903. During a term of years those in the 
laboratory well remember that he constantly discussed the 
feasibility of establishing a new journal. At the meeting of 
anatomists held in Baltimore, in 1900, a committee was formed 
to launch the American Journal of Anatomy, and its first 
number appeared the following Xovember, 1901. In 190fi 
followed the Anatomical Record, lioth published first in Balti- 
more. In 1908, when the Journal of Morphology was resumed 
by the Wistar Institute, Dr. Mall's work on monsters comprised 
its first number. In carrying out his ideas, however, he 
worked through others to such an extent that many failed to 
realize whose was the real directing force. His originality, 
far-seeing vision and courage for undertaking new enterprises 
could not be better illustrated than in these journals. More 
.striking still, as a sign of his ideal of developing scientific 
publications in this country are the new contributions to 
embryology, published by the Carnegie Institution of Wash- 
ington. 

In his introduction tn the article on His. Dr. ^Mall wrote 
these words : 

The ancient science of anatomy has been perpetuated during 
many centuries by great men who have dedicated their lives to it. 
The list is a long one, for the development of the science has been 
slow and progressive from the earliest ages to the present time: 
we find in it, on the one hand, some of the names of the greatest 
who have ever lived— Aristotle, Vesalius— on the other, the names 
of those who rank as leaders of a generation, Bichat, His. 



122 



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With Bichat and His belongs the name of Mall. His name 
will be associated with the present strongly physiological bent 
of modern anatomy, with the laying of a broad foundation of 
erganogenisis in embryology, whereby anatomy is being 
rationalized, and with the vision of a broadening of the scope 
of embryology so as to bring it into relation with the prob- 
lems of clinical medicine and social welfare. In America his 
place is unique, it goes without saying that he was our greatest 
anatomist. More than any other man in American medicine 
he has led his generation into the way of research. 

PUBLICATIONS OF 

FRANKLIN PAINE MALL. A.M.. M. D.. LL. D., 

Late Professor of Anatomy. Johns Hopkins I'niversily 

1. Entwickelung der Branchialbogen und Spalten des Huhn- 
chens. Arch. f. Anat. u. Entwickelungsgesch.. 1S87. 

2. Die Blut- und Lymphwege im Dunndann des Hundes. 
Abhandl. d. math.-phys. CI. d. k. Sachs. Gesellsch. d Wissensch., 
1887, XIV, 153-189. 

3. The first branchial cleft in the chick. Johns Hopkins Univ. 
Circulars, VII. 1888, p. 38. 

4. The branchial region of the dog. Ibid., p. 39. 

5. Development of the Eustachian tube, middle ear, tympanic 
membrane, and meatus of the chick. Studies Biol. Lab., Johns 
Hopkins Univ.. IV. 1887-8. 

6. The branchial clefts of the dog. with special reference to the 
origin of the thymus gland. Ibid. 

7. Reticulated and yellow elastic tissues. Anatomischer .\n- 
zeiger, 1888, III, 397-401. 

8. A study of the intestinal contraction. Johns Hopkins Hos- 
pital Reports, I, 1SS9. 37-75. 

9. Healing of intestinal sutures. Ibid.. 76-92. 

10. Reversal of the intestine. Ibid.. 93-110. 

11. Die motorische Nerven der Portalvene. Arch. f. Anat. u. 
Physiologie. 1890. Physiol. Abth., Sup. Bd.. 57-58. 

12. Development of the lesser peritoneal cavity in birds and 
mammals. Journal of Morphologj-, V, 1891, 165-179. 

13. Das reticulirte Gewebe und seine Beziehungen zu den Bin- 
degewebsfibrillen. Abhandl. d. math.-phys. CI. d. k. Sachs. 
Gesellsch. d. Wissensch., XVII, 1891. 299-338. 

14. A human embrj-o twenty-six days old. Journal of Morphol- 
ogy, V, 1891, 459-480. 

15. Methods of preserving human embryos. .-Vmerican Natu- 
ralist. 1891. 

16. Der Einfluss des Systems der Vena portae auf die Vertheilung 
des Blutes. Arch. f. Anat. u. Physiol.. 1892, Physiol, .-^bth.. 409-453. 

17. The vessels and walls of the dog's stomach. Johns Hopkins 
Hospital Reports, I, 1896, 1-34. 

18. A human embryo of the second week. Anatomischer An- 
zeiger, 1893, VIII. 630-33. 

19. Histogenesis of the retina in Amblystoma and Necturus. 
Journal of Morphology-, VIII, 1893. 415-432. 

20. Early human embryos and the mode of their preservation. 
Johns Hopkins Hospital Bulletin, IV, 1893. 115-121. 

21. Anatomical articles in the Supplement to the Reference 
Handbook of the Medical Sciences (coelom, human embrj-os, heart, 
thymus gland, thyroid gland, etc.), 1894. 

22. What is biologj? Chautauquan, XVIII, 1894, 411-414. 

23. The preservation of anatomical material for dissection. 
Anatomischer Anzeiger, 1896. XI. 769-775. 

24. The contraction of the vena portje and its influence upon the 
circulation. Johns Hopkins Hospital Reports, I, 1896. 

25. Reticulated tissue and its relation to the connective tissue 
fibrils. Ibid.. 171-208. 



26. The anatomical course and laboratory of The Johns Hopkins 
University. Johns Hopkins Hospital Bulletin, VII. 1896. 85-100. 

27. Papers from the Anatomical Laboratory of The Johns Hop- 
kins University (Editor), 1893-1896. Vol. I. 

28. Development of the human coelom. Journal of Morphology, 
XII, 1897, 395-453. 

29. Ueber die Entwickelung des menschlichen Darmes und 
seiner Lage beim Erwachsenen. Arch. f. Anat. u. Entwickelungs- 
gesch., 1897, Suppl.-Bd.. 403-434. 

30. Development of the ventral abdominal walls in man. Journal 
of Morphology, XIV. 1898. 347-366. 

31. Development of the human intestine and its position in the 
adult. Johns Hopkins Hospital Bulletin. IX, 1898, 197-208. 

32. The lobule of the spleen. Ibid.. 218-219. 

33. Development of the internal mammary and deep epigastic 
arteries in man. Ibid.. 232-235. 

34. The value of embryological specimens. Maryland Medical 
Journal. 1898. 

35. Book Review. " Lehrbuch der Vergleichenden mikroskop- 
ischen Anatomie der Wirbelthiere. Von Dr. Med. Albert Oppel." 
Science, N. S.. VII, 1898. 

36. Liberty in medical education. Philadelphia Medical Journal, 
III, 1899. 

37. Supplementarj- note on the development of the human 
intestine. -Anatomischer .Anzeiger, X^'I, 1899, 492-495. 

38. The architecture and blood-vessels of the dog's spleen. 
Zeitschr. f. Morphologic u. Anthropologic, II, 1900, 1-42. 

39. Preface: Hand Atlas of Human Anatomy, Spalteholz- 
Barker, I, Lippincott, 1900-1903. 

40. A contribution to the study of the pathology of early human 
embryos. From Contributions to the Science of Medicine dedi- 
cated by his pupils to William Henry Welch. Baltimore, 1900. 

41. Note on the basement membranes of the tubules of the kid- 
ney. Johns Hopkins Hospital Bulletin. XII. 1901, 133-135. 

42. On the origin of the lymphatics in the liver. Ibid.. 146-148. 

43. On the development of the human diaphragm. Ibid.. 158-171. 

44. On the development of the connective tissues from the con- 
nective-tissue syncytium. American Journal of .Anatomy. I. 1902, 
329-365. 

45. Note on the collection of human embryos in the anatomical 
laboratory of The Johns Hopkins University. Johns Hopkins 
Hospital Bulletin, XIV. 1903. 29-33. 

46. On the circulation through the pulp of the dog's spleen. 
.American Jour, of Anat., II, 1903, 315-332. 

47. On the transitory or artificial fissures of the human cere- 
brum. Ibid.. 333-339. 

48. Second contribution to the study of the pathology- of human 
embryos. From Contributions to Medical Research iVaughan), 
1903, 12-27. 

49. Catalogue of the collection of human embryos in the ana- 
tomical laboratory of The Johns Hopkins University. Baltimore, 
1904. 

50. On the value of research in the medical school. Michigan 
Alumnus, 1904, VIII, 395-397. 

51. Eight anatomical articles in Reference Handbook of the 
Medical Sciences, New Edition (coelom, comparative: ctelom, 
human: heart: human embryos, normal: human embryos, patho- 
logical: spleen: thymus: thyroid), 1904. 

52. On the development of the blood-vessels of the brain in the 
human embryo. .American Journal of Anatomy. IV. 1904. 1-lS. 

53. Wilhelm His. Ibid.. 1905, 139-161. 

54. On the angle of the elbow. American Jour, of .Anat., IV, 
1905. 391-404. 

55. Anatomical material: Its Collection and Its Preservation 
at The Johns Hopkins Anatomical Laboratory. Johns Hopkins 
Hospital Bulletin, XVI, 1905, 38-42. 

56. On the teaching of anatomy as illustrated by Professor 
Barker's .Manual. Ibid.. 29-32. 



May, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



123 



57. On some recent text-books of anatomy with special reference 
to the new American edition of Gray. Ibid.. XVII, 1906. 99-104. 

58. A study of the structural unit of the liver. Amer. Jour, of 
Anatomy, V. 1906, 227-30S. 

59. On ossification centers in human embryos less than 100 lUiys 
old. IbhI.. 433-45S. 

60. On some points of importance to anatomists. Remarks by 
the president at the twenty-first meeting of the Association of 
American Anatomists. Science, January 25, 1907. Republished in 
Anat. Record, I, Baltimore, 1907, 25-30. 

61. The collection of human embryos at The Johns Hopkins 
University. Anat. Record, 1907, I, 14-15. 

62. Papers from the Anatomical Laboratory of The Johns Hop- 
kins University, I-XI. 1S93-1906 (Editor). 

63. Book Review. " Review of Anatomy in America," by 
Charles Russell Bardeen. Anat. Record, 1, Baltimore, 1906. 

64. On measuring human embryos. Anat. Record, 1, Baltimore, 
1907, 130-144. 

65. Book Review. "Papers from the .\natomical I-aboratory of 
St. Louis University," by A. C. Eycleshymer. l-lll, 1904-6. Anat. 
Record, I, Baltimore, 1907. 

66. Book Review. " Contributions from the Anatomical Lab- 
oratory of Brown University," V, Providence, R. I., 1907. .\nat. 
Record, I, Baltimore, 1908. 

67. Book Review. " On Vogfs translation of Leopold's A Very 
Young Ovum in Situ." Anat. Record, II, Phila., 1908. 

68. On the teaching of anatomy. Anat. Record, II, Phila., 190S, 
pp. 313-335. 

69. Book Review. "On Bryce's Contribution to the Study of the 
Early Development and Embedding of the Human Ovum. .'^nat. 
Record, Phila., 1908, 265-268. 

70. A study of the causes underlying the origin of human mon- 
sters. (Third contribution to the study of the pathology of human 
embryos). Journal of Morphology, XIX, Phila., 1908, pp. 1-367. 

71. On several anatomical characters of the human brain, said 
to vary according to race and sex, with especial reference to the 
weight of the frontal lobe. Amer. Journ. Anat., IX, pp. 1-32, 
1909. Republished in Atlanta University, Publication No. 20. 1916. 

72. Book Review. " Die Xeue Anatomische Anstalt in Miin- 
chen." Von Dr. J. Riickert. Anat. Record, IV, Phila., 1910. 

73. A list of normal embryos which have been cut into serial 
sections. Anat. Record. IV, Phila., 1910, 357-367. 

74. Book Review^. '" Medical Education in the United States and 
Canada." By Abraham Flexner. Anat. Record, IV, Phila., 1910. 

75. Handbuch der Entwickelungsgescliichte des Mensclien. Hrs^ 
von Franz Keibel und F. P. Mall. 2 B. Leipz., 1910-11, S. Hirzel, 
559; 1045 p. 

76. Manual of Human Embryology. Edited by Keibel and Mall. 
2 v., Lippincott. Phila., 1910-1912. 

77. Report upon the collection of human embryos at The Johns 
Hopkins University. .■\nat. Record, V, Phila., 1911. pp. 343-357. 

78. On the muscular architecture of the ventricles of the human 
heart. Amer. Jour. Anat., XI, Phila., 1911, 211-266. 

79. On the development of the human heart. Amer. Jour. .-Vnat . 
XIII, Phila., 1912-13, 249-298. 

80. Bifid apex of the human heart. Anat. Record, VI, Phila., 
1912. pp. 167-172. 

81. Aneurysm of the membranous septum projecting into the 
right atrium. Anat. Record, VI, Phila., 1912. pp. 291-298. 

82. A plea for an institute of human embryology. Jour. Amer. 
Med. Assoc, LX, pp. 1509-1601. Chicago, 1913. 

83. An ovarian pregnancy located in the Graafian follicle. 
Surg., Gynec. and Obst., XVII, pp. 698-703. Chicago, 1913. 

84. Embryological Research. Year Book, No. 12, of the Carnegie 
Institution of Washington. Wash., 1913. 

85. Book Review. " University education in London." Science, 
N. Y., and Lancaster, Pa., 1913, n. s.. XXXVIII, pp. 33-39. 



86. On stages in the development of human embryos from 2 to 
25 mm. long. .Anat. Anz., Jena, 1914, XLVl, pp. 78-84. 

87. .\nnual Report of the Director of the Department of Em- 
bryology. Year Book, No. 13, of the Carnegie Institution of 
Washington. Wash., 1914. 

88. Scope and organization of the Department of Embryology. 
From " Scope an<I Organization of the Carnegie Institution of 
Washington." (Printed privately.) Baltimore, 1914. 

89. On the fate of the human embryo in tubal pregnancy. (Con- 
tributions to Embryology, No. 1.) Carnegie Institution of Wash- 
ington, Pub. 221. Wash., 1914. 

90. The cause of tubal pregnancy and the fate of the enclosed 
ovum. Surg., Gynec. & Obst., Chicago, 1915, XXXI, pp. 289-298. 

91. Development of the heart. Ref. Handb. Med. Sc, N. Y., 3d 
ed., V. pp. 58-65, 1915. 

92. Annual Report of the Director of the Department of Em- 
bryology. Year Book, No. 14, of the Carnegie Institution of 
Washington. Wash., 1915. 

93. The human magma r6ticul6 In normal and in pathological 
development. (Contributions to Embryology, No. 10.) Carnegie 
Institution of Washington, Pub. No. 224. Wash., 1916. 

94. On the study of racial embryology. Dept. of Embryology, 
pamphlet. (Printed privately.) Baltimore, 191G. 

95. Annual Report of the Director of the Department of Em- 
bryology. Year Book, No. 15, of the Carnegie Institution of 
Washin.gton. Wash., 1916. 

96. The embryological collection of the Carnegie Institution. 
Circular No. 18. (Printed privately.) Baltimore, 1916. 

97. Cyclopia in the human embryo. (Contributions to Embry- 
ology, No. 15.) Carnegie Institution of Washington, Pub. No. 226. 
Washington, 1917. 

98. Organization and Scope of the Department of Embryology. 
Circular No. 19. (Printed privately.) Baltimore, 1917. 

99. Note on abortions with letters from the Health Commis- 
sioner of Baltimore and from the Chief of the Bureau of Vital 
Statistics of Maryland regarding registration and shipment of 
embryos to the Carnegie Laboratory of Embryology at the J. H. 
M.S. Circular 20 (printed privately. ) Baltimore, 1917. 

100. On the frequency of localized anomalies in human embryos 
and Infants at birth. Amer. Jour. Anat., XXII. 1917, 49-72. 

101. Annual Report of the Director of the Department of Em- 
bryology. Year Book No. 16 of the Carnegie Institution of Wash- 
ington. (In press.) Wasli. 

102. On the a.ge of human embryos. Amer. Jour. Anat., 1918, 
XXIII, 397-422. 

103. With Dr. A. W. Meyer. (In preparation.) A survey of 
and studies on pathological ova in the Carnegie Embryological 
Collection. To be published in " Contributions to Embryology." 

104. With Dr. J. W. Williams. (In preparation.) Implantation 
of the human ovum. To be published In " Contributions to 
Embryology." 

SEPARATE MONOGRAPHS REPRINTED FROM THE 
JOHNS HOPKINS HOSPITAL REPORTS. 

Studlei In Dermatologr. Kj T. C. Gii.cuiu.st, M I> , and Esiurr Riz. 

FOKD, M. 1>. 1 vuluuie of 1U4 paties and 41 full-paije plal<?a. I'rice, 

bound lu paper, $3.00. 
Tha Malarial Fevers of Baltimore. By W. S. Tilwer, M. I>.. and J. 

Mewki.son, M.I). And A Study of some Fatal Cases of Malaria. 

Hy I.KWEI.LVS F. IUkkeb, M. B. 1 volume of iSO paKca I'rice. 

bound In paper. $'-.75. 
Pathology of Toxalbumin Intoxications. By Slmon Flexneb, M. l>. I 

volume of 15U pages wllb 4 fullpaKe lltboKrapba. I'rice, In paper, 

$2.00. 
Pneumothorax, A Historical. Clinical, and Experimental Study. By 

Charles p. EsirnsoN. .\l. D. I'rice. In paper, $4.00. 
Operations of 469 Cases of Hernia, In the Jobns Ilopklna Floapltal. from 

June, 188'.>. to Junuary. )S!)9. By Jos. f. BuoimoooD. M. D. Price. 

In paper, $3.00. 

Orders abould be addresBed tn 

Ihe Johns Honklns Press. Baltimore. Md. 



124 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 32: 



IN MEMOKIAM 

EDWIX S. LIXTOX 

Edwin S. Linton, a memVier of tlie class of 1918 of The 
Johns rio])kins Medical School, died in France on Xoveraber 
4, 1917. He was a son of Professor and Mrs. Edwin Linton, 
of Washington and Jefferson College, and a native of Penn- 
sylvania. He graduated at Washington and Jefferson College 
in 1913 and, after a year of post-graduate study at the same 
institution, entered The Johns Hopkins iledical School in 
1914, where he was an earnest and enthusiastic student until 
he became a member of The Johns Hopkins Hospital Unit 
and went to France. At first he was assigned to service at a 
port hospital for two months as a night superintendent, an 
admitting officer in the out-]mtient department, and in tlie 
operating room. 

Later, he rejoined the staff of the base hospital. After 
serving in various capacities, he finally was assigned to the 
medical service as an acting interne. 

Upon November 10, 191T, he fell ill with scarlet fever and 
died, four days later. His death was felt keenly by all, and 
especially by his classmates and associates, with whom he 
was a great favorite by reason of his ready wit and optimistic 
temperament. 

Flowers were sent by officers, nurses and fellow students. 
He was laid to rest on Xovember 15, 1917, with full military 
honors in the little French cemetery near Base Hos]iital Xo. 18. 

l.YLE BAITXES RICH 

Lyle Barnes h'ii li, a member of the class of 1918 of The 
Johns Hopkins Medical School, died of disease on December 
8, 1917, at Base Hospital No. 18, American Expeditionary 
Force, France, in his 26th year. He was one of a group of 
34 medical students who went to France in the summer of 1917 
in connection with The Johns Hopkins Hospital Unit. 

He was a native of Minnesota, a graduate of the University 
of North Dakota, and a student at The Johns Hopkins Medical 
School since 1914. He was an excellent student, being 
thorough and painstaking in all his work. Although quiet 



and reserved by nature, he was a sympathetic friend and wise 
counsellor to such as were in need of advice or assistance. 
He had an intuitive knowledge of human nature and a keen 
perception of character. He was fond of reading, of poetry, 
and also of music. He was a church memlier and a consistent 
Christian. 

While in France, he was for the most part assigned to 
laboratory work, largely in blood determinations and serum 
reactions, and proved himself to be a careful, painstaking and 
reliable observer. He was buried in the little hospital ceme- 
tery in France with military honors, attended by the whole 
personnel of the Unit, by the side of his classmate, Edwin S. 
Linton. 

MIRIAM K. KXOWLES 

iliriam E. Knowles, daughter of ilr. and ilrs. Thomas C. 
Knowles, of Yardley, Pennsylvania, died November 12, 1917, 
at Base Hospital No. 18, American Expeditionary Force, of 
scarlet fever, after an illness of five days. 

Miss Knowles was a graduate of Wellesley College and of 
The Johns Hopkins Hospital Training School for Nurses, 
class of 1916. She was an enthusiastic member of The Johns 
Hopkins LTnit, interested in her work, and devoted to her 
patients; and they to her. Each day in her roxmd of duties, 
she seemed to find another reason why she was glad to be con- 
sidered among the first on duty in France, ready to serve her 
country. 

She was buried with other Americans in a little French 
cemetery very near Base Hospital No. 18. Simple, but im- 
))ressive, ceremonies were conducted by a clergyman connected 
with the Y. M. C. A. " Lead Kindly Light," the most loved of 
hymns, was beautifully sung by a quartette of medical students. 
The nurses attended in Red Cross uniforms. The officers 
acted as pallbearers, with the entire personnel as escort. Her 
casket was draped with the American flag. There were many 
floral oft'erings from nurses, officers, students, and her friends 
among the patients. Every possible honor was shown her as 
she was laid to re.st by those who had learned to know and 
appreciate her for what she was — a loyal friend and a devoted, 
conscientious nurse, who had given her life for her countrv. 



NEW PUBLICATIONS. 



The following six monographs : 

Free Thrombi and Ball-Thrombi in the Heart. By J. H. 
Hewitt, M. D. 82 pages. Price, $1.00. 

Benzol as a Leucotoxin. By L.*.urexce Selling, M. D. 60 
pages. Price, $1.00. 

Primary Carcinoma of the Liver. By M. C. Wixtehnitz, 
M. D. 42 pages. Price, 75 cents. 



The Statistical Experience Data of The Johns Hopkins Hos- 
pital, Baltimore, Md., 1892-1911. By Frederick L. 
HoFFMAX, LL.D., F.S.S. 161 pages. Price, $2.00. 

The Origin and Development of the Lymphatic System. By 
Florence K. S.\bin. 94 pages. Price, $2.00. 

The Nuclei Tuberis Laterales and the So-called Ganglion 
Opticuni Basale. By Edward F. Malone, M. D. 
Price, $1.50. 



are now on sale by The Johns Hopkins Press, Baltimore. Other monographs will appear from time to time. 



May, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



125 



NOTES ON NEW BOOKS. 



The Pathology of Tumors. By E. H. Kettle, M. D., B. S., Lond. 
Cloth ?3.00. (^'elo York: Paul B. Hoeber, 1916.) 

This small volume will be appreciated by the student of micro- 
scopic surgical pathology who may easily, to say the least, be 
perplexed by the mass of diverse, uncorrelated nomenclature which 
abounds concerning tumor pathology. Adoption of the older no- 
menclature seems not unwise, since a knowledge of synonyms 
cannot be avoided and the older terms may better be learned first. 

The number and quality of the microscopic illustrations in them- 
selves make the book desirable and valuable; whereas its brevity 
does not bar its usefulness as a handy volume of reference. Its 
avowed almost total abstinence from reference is regrettable. 
The value to the student of such a book, in which some concrete 
idea of the structure of almost any given tumor is quickly to be 
visualized, would certainly be greatly enhanced if there were 
present a list of the related noteworthy publications. The scope 
of such a book as this can only be to furnish nuclei for more com- 
plete units of information. The fact, as the author notes, that 
Durante first enunciated the theory of embryonic rests, usually 
attributed without qualification in this country to Cohnheim, 
would be made of more interest to the student if the reference 
were at hand. This is a less vital instance of the failure of this 
time-saving plan of little or no bibliography. 

The management of the subject matter is simple. In the first 
part is placed a summary of the various phases of the general 
biology of tumors; next the general, and thirdly the special pa- 
thology of tumors receives attention. The description is clear and 
concise. However, the notice given certain glands, for instance, 
the pituitary, is far too scanty. The book fills a niche in the 
domain of surgical or tumor pathology reference books, although 
its limitations are easily seen. Not the least of the latter is its 
almost total omission of macroscopic considerations. It is, how- 
ever, an efficient presentation of many of the " chief points " of 
microscopic tumor pathology, and should be a handy book for 
every second and third year student. W. C. D. 

Finch and Baines: A Seventeenth Century Friendship. By Archi- 
HALU Malloch, B. a. (Queens); M. D. (McGlll); Temporary 
Captain, Canadian Army Medical Corps. (Cambridge: At the 
University Press, 1917.) 

This charmingly written and beautifully printed quarto of 89 
pages, with 9 full-page photogravure illustrations, owes its incep- 
tion, if we are to credit the author, to the suggestion of Sir William 
Osier, who has given such an impetus to medical biographical 
studies in America and England. The lapse of years does not 
render it difficult for the writer of this brief review to remember 
" Archie Malloch " as a boy under surgical treatment at The Johns 
Hopkins Hospital, and to recall his acute mind and his keen 
interest in the better forms of literature. It is not strange that 
in after years he should have developed a fondness for the studies 
which have given us this volume. 

The Seventeenth Century Friendship relates the story of the 
intimacy between Sir John Finch (1626-1682) and Sir Thomas 
Baines (1622 or 24-1680). Both were medical men and graduates 
of Cambridge University, which in the troublous times of the 
period seems to have been preferable to Oxford as a place of study. 
Both journeyed to Italy together and spent some years at Padua 
and received degrees there. They later resided at Pisa, where 
Finch occupied the Chair of Anatomy in the university there under 
the patronage of the Grand Duke of Tuscany, and remained several 
years. He had as associates such men as Malpighi, Steno, Borelli 
and other famous names. Upon Finch's return to England he 
was made a physician to the Queen, was knighted by Charles II 
in 1661, and later sent as an ambassador to the Duke of Tuscany. 



His friend Baines was also subsequently knighted, and appointed 
a professor of music at Gresham College. Both Finch and Baines 
were among the original charter members of the Royal Society of 
England. 

Notwithstanding a decided scientific attitude of mind towards 
natural phenomena. Finch was not always free from a certain 
amount of unscientific credulity. He believed that on one occasion 
a shower of wheat occurred in Italy, and also that the pictures on 
the walls of a church on certain feast days descended from the 
walls of their own motion. He also became interested in the 
case of a blind man in Holland who claimed to have the ability 
to detect color by touch. Finch seems to have had a degree of 
incredulity about him, but does not avow his utter disbelief in 
the possession of such power. The friendship of Finch and Baines 
seems to have been most intimate. Baines accompanied Finch to 
Constantinople when the latter was made ambassador, and died 
there; his remains were brought to England by Finch on his 
return. 

Finch never married, it is thought, out of consideration for the 
wishes of Baines. The friendship between the two was most 
cordial and each seems to have supplemented the qualities of the 
other. Neither were great physicians or investigators, but both 
were interested in studies which were common to medical men 
at those times. They were eager for curious bits of natural his- 
tory and semi-scientific knowledge. Finch seems to have been the 
best anatomist and man of science; Baines, on the other hand, was 
the better philosopher and broader thinker. The letters so freely 
printed which passed between Finch and his sister, Anna Conway, 
and other relatives threw much light upon contemporary history, 
manners and customs. The volume also shows the debt of English 
medical study, especially in anatomy and chemistry, to Italy in 
the 17th century. The author deserves great praise for the pains- 
taking and admirable use which he has made of his materials. 

H. 

A Text-Book of Nervous Diseases for Students and Practising 
Physicians. In thirty lectures. By Robebt Bixg. Translated 
by Charles L. Allen. Cloth. (New York: Rebman Company, 
1!)1.-,.) 

As the translator states in his preface, this is a thoroughly use- 
ful, practical and up-to-date book. Both the student and the prac- 
titioner should find it so. In size between the summary compends 
and the larger handbooks, it is convenient to handle, the type is 
good and the illustrations are excellent. 

The subject matter is well arranged and well presented. It 
would be even more attractive had the translator followed less 
closely the original German phraseology. 

The nervous manifestations of arteriosclerosis are especially 
well treated. T. P. S. 

Diseases of Occupation arid Vocational Hygiene. Edited by 
George M. Kober, M. D., and William C. Hanson, M. D., with 
illustrations and reference tables. Cloth $8.00. (Philadel- 
phia: P. Blakiston's Son d- Co., ll>l(i.) 

No one connected with an active out-patient clinic in a large 
manufacturing community can tail to be impressed with the fre- 
quency with which occupational diseases are met with, owing to 
the fact that very often adequate protective measures are not 
instituted in many manufacturing establishments. Fortunately, 
the more enlightened manufacturers are gradually becoming alive 
to the importance of protecting their workmen a.gainst intoxica- 
tions of various kinds, partly from humanitarian motives and 
partly owing to the fact that failure to do so has taught them that 
they lessen the industrial efficiency of their employees. This volume 



126 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 3-i 



is, therefore, very timely, since it brings up to date the knowledge 
that has been acquired concerning the various occupational dis- 
eases, as well as the best measures for preventing them. No 
dispensary, public health official, social worker, corporation sur- 
geon, or director of a manufacturing plant, where the health of 
its employees is endangered, should be without this modern 
treatise. 

The editors, the senior member of whom has done so much for 
the furtherance of industrial hygiene in this country, in a pre- 
fatory note, give a most interesting historical account of what 
has been done up to the present time towards preventing industrial 
diseases among workmen engaged in menacing occupations. 
England was the pioneer nation to grapple with this important 
problem, followed by France, Germany and the United States. 
Much useful legislation has been enacted in these countries to 
lessen the menace from various dangerous trades. 

The work is really a collection of monographs by specialists in 
their particular lines. The authors are John B. Andrews, Irene 0. 
Andrews, George L. Applebach, Bailey K. Ashford, Clarence J. 
Blake, John T. Bowen, Louis Casamajor, C. H. Crownhart, Luigi 
Devoto, Seward Erdman, Langdon Frothingham, Alice Hamilton, 
Emery I-layhurst, Charles R. Henderson, Frederick L. Hoffman, 
Frederick S. Lee, Thomas S. Lee, Thomas M. Legge, Harry Lilien- 
thal, Owen R. Lovejoy, Sir Thomas Oliver, Thomas Ordway, Harry 
C. Soloman, Elmer E. Southard, Ludwig Teleky, John W. Trask. 
Ernest E. Tyzzer, George C. Whipple and H. V. Wiirdemann. 

The editors have divided the subject matter into three parts. 

Part I deals with the specific and systemic diseases of occupa- 
tion, including fatigue and the neuroses. 

Part II deals with the causation and prevention of occupational 
diseases and accidents. 

Part III is intended to be of service to those who may be called 
upon to investigate in the shop or factory, and in the dispensary 
and hospital, the relations of occupation to disability and disease. 

For two decades Thomas Oliver's " Dangerous Trades; The 
Historical, Social and Legal Aspects of Industrial Occupations 
as Affecting Health " has served a most useful purpose as a work 
of reference. The present work, to which Sir Thomas Oliver is 
a contributor, brings our knowledge of occupational diseases 
thoroughly up to date. T. B. F. 

Soma Personal Reminiscences of Dr. Janeway. By Ja.mks B.w.mui 
Clahk, M. D. (New York: O. P. Putnam's Sons, 1'.)I7.) 

This tribute to the late Dr. E. G. Janeway by an intimate friend 
is marked by a sincere desire on the part of the author to portray 
him' as he knew him in his daily life in contact with patients and 
students, and in his professional studies and public life. Dr. Clark 
gives many interesting reminiscences of acts of kindness towards 
the sick and deserving, and anecdotes of a personal character 
showing Dr. Janeway's manner of life and modes of thought. He 
was kind in his relations with young and inexperienced physi- 
cians; he loved his profession, and was high-minded in the per- 
formance of all duties; he strove to advance the science of medi- 
cine by his labors and studies. The gratitude of the author to 
Dr. Janeway is most creditable, and forms in reality the key-note 
of the little book. 

The Obstetrical Quiz for Nurses. By Hilda Emzaukth Caklson. 
Cloth ?1.75. (New York: Rehman Company, int.').) 

In writing this "monograph on obstetrics" the author has 
placed before pupil nurses the first obstetrical quiz compend writ- 
ten for their special needs. For some time the necessity for such 
a book has been apparent and this work is an excellent attempt 
to supply this need. In the instructive question and answer form 
it covers the essentials of obstetrical anatomy, physiology, and 
pathology. A very good feature is the attention given to the 



proper methods in emergencies arising in obstetrical practice at 
homes. 

The chapters on anatomy, physiology, and normal labor are 
especially well written and the lists of supplies given in Chapter 
VI should prove of great value to nurses undertaking the care of 
obstetrical patients at home. The chapter on the new-born child 
is valuable, as the average nurse knows tar too little about the 
less important of her two patients. 

There are a few undesirable features about the book. The 
advice to nurses to attempt replacing a prolapsed cord by intra- 
vaginal manipulations is not good. The two last chapters on 
anaesthesia seem uncalled for and out of place in the book and 
it is to be hoped that they will be omitted from future editions. 
The first of these on scopolamine-morphine ansthesia is admittedly 
a copy of the report of Rongy and Arluck published in the New 
York Medical Journal in September, 1914, and its presence in this 
book will doubtless be of assistance in the propaganda for " twi- 
light sleep," a procedure that has been given up almost entirely. 
The last chapter on nitrous oxide anaethesia is compiled from the 
reports of several men and is the poorest part of the book. 

Although a casual reader may think this book too voluminous and 
condemn it because of much detailed matter, it is this very atten- 
tion to minutiae that should make the obstetrical quiz of invaluable 
assistance to the obstetrical nurse. J. G. M., Jr. 

Operations on the Bones. Joints, Museles and Tendons. By Rouekt 
SoiTTER, M. D, Cloth $4.50. (Neiv York: The Macmillan 
Company, I'.in.) 

This book considers the various orthopedic procedures, region- 
ally, in a very satisfactory way. The methods outlined are given 
completely and in great detail. The cuts are diagrammatic and 
clear, not handicapped by any attempt at artistic display. The 
book is extremely well gotten up for the " occasional orthopa>dist." 

Certain general procedures are repeated in detail each time 
reference is made to them, as in arthroplasty, overlapping frac- 
tures, methods of drainage, etc. This seems unessential. 

There seems to be too much emphasis laid on the use of silk as 
tendon extensions in muscle transplantations, as, for instance, at 
the knee, where the hamstrings may be anchored directly to the 
patella, avoiding the complicated technique of silk extension to 
the patella and tibia. I. Z. 

Embryolofiy. Aitatomy. and Diseases of the Vmbilicus, Together 
ivith Diseases of the Urachus. By Thomas Stki'HKN Cillex. 
Associate Professor of Gynecology in The Johns Hopkins 
University and Assistant Visiting Gynecologist to The Johns 
Hopkins Hospital. Illustrated by Max Brodel. {Philadelphia 
and London: W. B. Saunders Company, I'.HH.) 

The delay in giving an earlier review of this monumental work, 
due to unforeseen, regrettable and irremediable accidents, renders 
a fresh detailed review unnecessary now. The book bears lasting 
testimony to the ability, scientific zeal and great industry of the 
author, who has performed his self-appointed task so well that one 
feels that the same intensive work will never need to be done again. 
The volume is an exhaustive presentation of a group of hitherto 
obscure diseases, and contains 680 pages with 269 figures in the 
text and 7 full-page illustrations. 

It seems, however, to the reviewer a fitting time to add for 
the benefit of the readers of the Bulletin, many of whom are 
especially interested in the work and its author, extracts from 
some of the reviews which have appeared elsewhere, as showing 
the reception accorded to it by surgeons and pathologists. 

The Lancet. London, says: "This book, however, deals not 
only very fully with all tlic known diseases of the navel, but also 
with such other matters as the omphalomesenteric duct and ves- 
sels, Meckel's diverticulum, and the urachus. The importance of 



May, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



127 



the embryology of the umbilicus is very considerable because so 
many of the lesions are due to a partial or complete lack of closure 
of the omphalomesenteric duct or of the urachus. The section 
devoted to this subject is extremely clear, and is illustrated by 
a very fine series of drawings by Max Brodel. The many inter- 
esting and instructive points which a detailed study of the anatomy 
reveals are well set out in Capter II, and the four plates showing 
the different forms of the umbilicus will be a revelation to those 
who have never studied this region particularly. Umbilical in- 
fections and hemorrhage in the new-born child happily have lost 
the importance they once had, but an account of many of the old 
epidemics is given by the author and their relation to infections 
of the umbilical stump clearly shown. A large number of cases 
of the curious tumors, formed by remnants of the omphalomesen- 
teric duct, the so-called umbilical polyp, are collected and given 
in full, while the chapters dealing with a patent omphalomesen- 
teric duct and prolapse of the bowel through such a duct are most 
interesting. As the author rightly points out, when a small 
umbilical polyp is noted after the cord has come away, the probable 
persistence of other portions of the omphalomesenteric duct, such 
as a Meckel's diverticulum or a cord from the mesentery to the 
umbilicus, must be remembered, and the added possibility of 
intestinal obstruction developing later in life explained to the 
parents. It is interesting to find that most of the cases of so-called 
dermoids of the umbilicus turn out on further investigation to 
be nothing more than inflammation due to the irritation of an 
umbilical concretion, the presence of caseous material and wool 
from the patient's clothing having led to an erroneous diagnosis 
in many of the cases. Records of cases of Paget's disease, diph- 
theria and syphilis of the umbilicus are given, and also numerous 
cases illustrative of the escape of intra- and extra-abdominal 
fluid, mostly pus, through the umbilicus as well as cases of 
umbilical flstulae. 

" Among the most curious of all the conditions described is 
the series collected by Dr. Cullen of umbilical tumors containing 
uterine mucosa or remnants of Miiller's duct, in reality adeno- 
myomata of the umbilicus. It was a case of carcinoma of the 
umbilicus which first led the author to a study of the whole sun 
ject, and the chapter on that condition contains the records of 
many cases of both primary and secondary carcinoma of this 
region." 

The EdinhurgU Medical Journal says: "The author confesses 
that up till the year 1904 he had thought that hernia was prac- 
tically the only lesion to be noted in this locality. A chance case 
of cancer of the umbilicus, which he happened to meet with in his 
practice, sent him to the library in search of any records extant 
of a similar condition. He was astonished at the wealth of 
material on the umbilicus which he found scattered throughout 
the literature of surgery, and decided to collect and analyze it. 
The result of his labors astonishes us. His investigation has been 
most thoroughly done — the mere assembling of the literature to 
the end of 1912 took three years — and, with the aid of a number 
of collaborators, he has summarized what had been written up to 
that date so completely that no one need go further than his pages 
to find the gist of what has previously been written on the subject. 

" With the aid of a series of excellent diagrams made by Max 
Brodel the description of the embryology of the umbilical region 
is rendered perfectly clear, and the understanding of the various 
congenital defects that are later described is greatly facilitated. 
The section on the anatomy of the umbilicus is illustrated by four 
plates containing 60 drawings of ' normal umbilici,' no two of 
which bear more than a superficial resemblance to one another. 
In fact, the differences are so marked that it is difficult to conceive 
a normal type. The author, indeed, has had to divide them into 
no fewer than nine groups. 

" A chapter is devoted to umbilical infections in the new-born, 
each farm of infection being illustrated with notes of a few 



typical cases. Umbilical hemorrhage is dealt with in a most in- 
structive and useful way. The numerous conditions associated 
with aberrations of the omphalomesenteric duct are fully described 
and profusely illustrated, as are also those of urachal abnormali- 
ties. Among other chapters of real clinical value are those on 
umbilical concretions, tumors and infective granulomata. 

" As we have already indicated, this work represents an enor- 
mous amount of literary research, as well as pathological and 
clinical observation, and it forms a valuable source of reference." 

The American Journal of Obstetrics and Diseases of Wometi and 
Children says: " It represents the result of eight years of inten- 
sive and scrupulously careful research work. The assembling of 
the literature of the subject alone and its critical study took all 
of three years, and was made possible only by the facilities of the 
Surgeon-General's Library at Washington. As an example of 
the care taken in its production, when the book was set up in 
galley, the author, realizing that the tremendous number of cases 
mentioned would be most valuable with the fewest chances of 
error, had the entire book checked off with the original articles. 
Subsequent writers can accordingly feel safe in relying on the 
accuracy of the cases recorded." 

The Boston Medical and Suryical Journal says: " It constituted 
a really complete survey of the literature upon the umbilicus and 
urachus, with the exception of umbilical hernia, and this survey 
is enriched with a large amount of original observation. Three- 
quarters of the volume are devoted to the umbilicus, one-fourth 
to the urachus, and the whole profusely illustrated with 269 text- 
figures and 7 plates, many of them original and some colored. 
The work is one of the best Teutonic type of thoroughness and 
value, written by an American in a charming and delightful En- 
glish literary style, unusual among physicians." 

The Americati Journal of the Medical Sciences says: " Perhaps 
it is the very portliness of the volume, perhaps it is merely a 
habit of much writing acquired during its preparation, that in- 
spired the author with the idea of condensing its contents into 
a preface of some three thousands words. We urgently counsel 
those who may contemplate, as we fear some hardy souls may, the 
perusal of the entire volume from cover to cover, to begin sys- 
tematically with the preface. Then to follow the advice therein 
to study (not merely to admire) the illustrations of embryology: 
and then (but this advice is not in the preface) to lay the volume 
carefully away upon its shelf, to be called upon as a work of 
reference whenever needed — and this, we predict, will not be very 
often. 

"The plan of the work is all inclusive; embryology, anatomy; 
umbilical infections in the new-born; remnants of the omphalo- 
mesenteric duct; congenital polyps; Meckel's diverticulum; in- 
testinal cysts; umbilical concretions; purulent and fecal fistulEe 
at the umbilicus; umbilical hernias; umbilical tumors; patent 
urachus; urachal cysts — these are but a few of the chapter head- 
ings, for the volume treats de omnibus rebus et guibusdam aliis. 
Not only are the history, the pathology, the symptoms, the diag- 
nosis, the prognosis and the treatment of each condition given at 
length, but there is appended nearly to every section a long list of 
case abstracts, alphabetically arranged according to the author's 
name, which have been disinterred from former and less worthy 
sepulchers to be reinterred with befitting pomp and splendor in 
this magnificent mausoleum." H. M. H. 

Bibliography of William Henry Welch. M. D.. LL.D. Prepared by 
W.\LTER C. BuRKET, M. D., of The Johns Hopkins University. 
(Baltimore: The Johns Hopkins Press, lan.) 

This attractive volume of 47 pages has been prepared by Dr. 
Burket as a part of a larger scheme to collect and publish the 
papers of Dr. Welch scattered throughout the medical literature 
of the world. This remarkable collection of titles shows how much 



128 



JOHXS HOPKINS HOSPITAL BULLETIX 



[Xo. 32} 



material is at present buried in periodicals, transactions, reprints 
or manuscripts which deserves publication in a collected form 
readily accessible to students and teachers of medicine. The 
preparation of this volume has involved much care and painstak- 
ing search on the part of the compiler, who deserves the thanks 
of all physicians for his altruistic labors. After an examination 
of the wealth of material to which it is an index, one feels that the 
publication of the larger collection ought not to be indefinitely 
delayed. H. M. H. 

International Clinics: A Quarterly of Illustrated Clinical Lectures 
and Especially Prepared Original Articles on Treatment, itedi- j^ 
cine. Surgery, yeurology. Pa-diatrics. Obstetrics. Gynecology. 
Orthopwdics. Pathology. Dermatology. Ophthalmology. Otol- 
ogy. Rhinology. Laryngology. Hygiene, and other Topics of 
Interest to Students and Practitioners. By Leading Members 
of the Medical Profession throughout the World. Edited by 
H. R. M. Landis, M. D., Philadephia, U. S. A. {Philadelphia 
and London: -J. B. Lippincott Company.) 

Owing to the great variety of the papers in the rapidly recur- 
ring volumes of the international clinics, it is not practicable to 
give any review in detail of them. The papers vary, it is true, in 
excellence and execution, but all make special appeal to some 
members of the medical profession, and hence are of value. The 
titles mentioned below, however, will give some conception of 
the scope of the papers and the appeal to one reader at least. 

26th Series, 1916, Volume IV. 

" Insomnia as a Dread," by James J. Walsh, M. D., New York. 

" Duodenal Ulcer in Infancy," by Henry F. Helmholz, M. D., Chi- 
cago, 111. - . 

" The Psychologj- of the Criminal under the Sentence of Death," by 
Paul E. Bowers, M. D., Michigan City, Indiana. 

27th Sekies, Volume I. 

" The Tangled Skein," by J. Madison Taylor, M. D. 
" Health Efficiency of Workers Due to their Living Conditions," by 
H. R. M. Landis, M. D. 

27th Series, Volume 11. 

" Gout and Infectious Arthritis," by Henry A. Christian, M. D. 

•' Tj-phoid Fever with Complications," by Lewellys F. Barker, M. D. 

" Jaundice with Enlarged Liver in a Young Adult," by Thomas 

McCrae, M. D. 
" A Group Study of the Results of One Hundred Physical and 

Mental Examinations of So-Called Well Children," by William 

R. P. Emerson, M. D. 
" Skin Grafting " by Arthur M. Shipley, M. D. 
"Giovanni Maria Lancisi (1654-1720)," by John Foote, M. D. 

27th Series. Volume III. 

"Concerning the Etiology of Iridocyclitis, with Special Reference- 

to Local Infections," by George E. de Schweinitz, M. D. 
" Chronic Nephritis, with a Discussion of Functional Tests," by 

Henry A. Christian, .M. D. 
•■ Lectures on Intracranial Hemorrhage," by Charles Greene Cum- 

ston, M. D., Geneva, Switzerland. 
■' A Study of Arterial Blood Pressures, with Reference to their 

Clinical Values." by Thomas E. Satterthwaite, M. D. 
" Neurasthenia Before and After the War," by James J. Walsh, 

M. D. 



" Observations Regarding the Operative Treatment of Selected 
Cases of Cerebral Spastic Paralysis Due to an Intercranial 
Hemorrhage at Birth," by William Sharpe, M. D. 

27th Series, Volume IV. 

" Compound Comminuted Fracture of the Tibia and Fibula from 
Railroad Injury, etc., by Arthur Dean Bevan, M. D. 

" Two Lectures on Injuries to the Cranium and the Brain in War- 
fare," by Charles Greene Cumston. M. D. 

" Some Food Facts for War Time Consideration," by Gordon J. 
Saxon, M. D. 

Clinical Cardiology. By Seliax Neuhof, B. S., M. D. Cloth $4.00. 
(Neic York: The ilacmillan Company. 1917.) 

As its name indicates, " Clinical Cardiology " is written pri- 
marily from the clinical standpoint. The first third of the book, 
which deals with the anatomy and physiology of the heart, in- 
strumental methods of examination, and the arrythmias, is concise, 
though this conciseness leads at times to a somewhat dogmatic 
treatment of controversial matters, as for instance, the description 
of the course of the excitation wave in the ventricle. The experi- 
mental and pathological work on which the interpretation of 
graphic records is based, receives scant attention. The portion 
dealing with the arrythmias is profusely illustrated, clear, and 
up to date. The passage on the displacement or hypertrophy of 
the heart, and the form of the electrocardiogram is excellent, and 
the author's views on splitting of the P and R waves are of interest. 
Throughout this portion of the book care is taken to correlate 
clinical signs with graphic records. 

The chapter on orthodiascopy is much needed. Perhaps the 
most valuable part of the book is that on physical examination, 
on which are brought to bear a great many resources not com- 
monly appreciated. The author's distrust of percussion outlines 
will be shared by all those who have access to the X-ray even 
if his " rational method " fails, because of its indirectness, to meet 
with favor. 

The chapters on endocarditis, myocarditis and cardiac syphilis 
embody much valuable material, formerly accessible, if at all, only 
with difiiculty. That on myocarditis and coronary sclerosis has 
the same merit and is probably as clear as the present state of 
our knowledge on these subjects will admit. Intraventricular con- 
duction defects might have well been mentioned in this connec- 
tion. Recent attempts at exact measurement of the cardiac re- 
serve are dismissed in a page, as inferior to general clinical ob- 
servations before and after exercise, yet at least one such measure- 
ment promises to be of value, namely, Peabody's estimation of 
the cardiac reserve by means of the vital capacity of the lungs. 
The remainder of the book is devoted to miscellaneous topics, 
cardiotherapy, renal tests in cardiac disease, the management of 
cardiac disease, blood pressure, weak heart, precordial pains, and 
therapy of the circulation in pneumonia. 

The arrangement of the book might be improved, in spite of the 
difficulty caused by the variety of topics necessarily included. .\ 
fairly extensive bibliography with few important omissions is 
appended to each chapter, which would have been more useful 
but for the conspicuous lack of references to specific authors 
throughout the text. Those who desire a detailed knowledge of 
the physiolo.io' of the heart, normal and pathological, or of its 
pathological lesions will fare better elsewhere. Those who appre- 
ciate the work of a keen and original clinical observer on the cir- 
culation as viewed from the clinical standpoint, with sufficient 
description of graphic methods to make the volume intelligible, 
will find it both stimulating and valuable. H. B. R. 



The Johni) Hopkins Hospital Bulletins are issued monthly. They are printed bii the LORD B.i.LTIilORE PRESS. Baltimore. Subscriptions. $3.00 
a year (toreign postage, 50 cents), may be addressed to the publishers, THE JOHS!? nOPKIS.'! PRES.'?, BALTIUORE ; single copies tcill be sent by 
mail tor fifty cents each. Single copies may also be procured from the BALTIMORE XEWS CO., Baltimore. 



BULLETIN 



OF 



THE JOHNS HOPKINS HOSPITAL 



Entered as Second-Class Matter at the Baltimore, Maryland, Postofflce 



Vol. XXIX— No. 328] 



BALTIMORE, JUNE, 1918 



[Price, 50 Cents 



CONTENTS 



The Effect of Forced Feeding on the Xitrowen Equilibrium and 
the Blood in Pernicious Anemia. 

By Herman 0. Mosexthal 129 

The Clinical Significance of the Irregular Distribution of Vari- 
ous Cells and Parasites in the Blood Stream and the Pro- 
duction of Abortive Leukiemic Changes and of Splenomegaly 
in the Maeacus Rhesus. (Illustrated.) 
By Andrew Watson Sellaeds and Walter Albert 

Baetjer 135 

Memorial Meeting to Dr. Theodore Caldwell Janeway. (Illus- 
trated.) 142 

Dr. John Hall: Shakespeare's Son-in-Law. (Illustrated.) 

By Eli Moschcowitz, A. B., M. D 148 

Proceedings of Societies. 

The Johns Hopkins Hospital Medical Society 152 

Demonstration of a Duodenectomized Dog. (Abstract.) 
[Dr. Ernest G. Gray] ; — The Origin of the Corpus Luteum 
[Db. G. W. Corner] ;— On the Absorption of Drugs and 



Poisons from tlie Vagina. (Abstract.) [Dr. David I. 
Macht] ; — On the Absorption of Drugs from the Urethra, 
Bladder, Ureters and Pelvis of the Kidney. (Abstract.) 
[Dr. David I. Macht] ; — Cinq ans Apres [Dr. F. C. Shat- 
tdck] ; — Exhibition of a Case of Internal Hydrocephalus 
[Dr. W. E. Dandy] ; — Visits to Cantonments. (Abstract.) 
[Dr. Welch]; — A Xew Hypophysis Operation [Devised by 
Db. G. .J. Heuer. Presented by Dr. W. E. Dandy, in Dr. 
Heuer's Absence] ; — Observations upon the Pathology of 
Diabetes [Dr. Frederick M. Allen] ; — Results of Past 
Methods and To-Day's Problems in the Treatment of Dia- 
betes [Dr. Elliott P. Jo.slin]. 
The Johns Hopkins Hospital Historical Club .... 155 
The Historical Section of the Royal Society of Medicine in 
London. (E.xtract from Dr. Futcher's Letter to Dr. Hurd, 
December IC, 1917.) 

Notes on New Books 156 

Books Received 156 



THE EFFECT OF FORCED FEEDING ON THE NITROGEN EQUILIBRIUM 
AND THE BLOOD IN PERNICIOUS ANEMIA 

By Herman 0. Mosenth.\l 
(From the Medical Clinic of The Johns Hopkins Hospital) 



Forced feeding has always been relied on as an important 
aid in the treatment of pernicious anemia. This form of therapy 
is based on the common idea that wef\k and feeble individuals 
become healthy and strong if they receive a generous amount 
of nourishing food. Such a conception has no scientific foun- 
dation and yet it is the only one on which the present day use 
of diet in this disease rests. Prolonged feeding experiments 
in which the diet has been accurately weighed and calculated 
are lacking and the skepticism of many physicians in regard 
to the value of diet in pernicious anemia evidently depends 
largely upon circumstantial evidence and not upon accurate 
observations. 

If a high diet is to be of benefit to a case of pernicious 
anemia, it should bring about at least two results : First, there 
should be an assimilation of protein by the body, or, measured 
in terms of nitrogen, there should be a positive nitrogen bal- 
ance; second, the red blood cells and hemoglobin should 
increase. The present article deals with three cases of perni- 



cious anemia who were put on forced feeding for about one 
month and studied with the above points of view in mind. 
It was originally intended to make this work much more 
extensive, but inasmuch as under the present circumstances it 
will have to be discontinued indefinitely, the cases observed thus 
far are reported at this juncture, as they prove certain points 
in regard to the relation of diet to pernicious anemia. 

Some doubt still exists as to whether or not it is possible 
to effect an assimilation of protein in pernicious anemia and 
allied conditions. Pearce (1) has recently made the follow- 
ing excellent summary of the status of this question: 

From a review of the literature it is evident that in anemia, 
with or without splenic disease, the majority of investigators 
have experienced diflHculty in obtaining a nitrogen balance. Umber 
(2), in his study of Banti's disease; Minot (3), in pernicious 
anemia; McKelvy and Rosenbloom (4), in congenital hemolytic 
icterus, and Rosenqvist (5), in pernicious anemia and bothrio- 
cephalus anemia, all report a pathologic destruction of protein. 
Umber (6) goes so far as to urge this "toxic destruction" as a 



130 



JOHNS HOPKINS HOSPITAL BULLETIN 



[Xo.. 328 



criterion tor operation. Von Noorden (7) alone opposes this theory 
of increased destruction of protein in anemia. In the two cases 
we report, no difficulty was experienced in obtaining a positive 
nitrogen balance before operation: feeding was not forced, the 
patients merely satisfying their natural desires for food. Never- 
theless, the increased retention, immediately after the operation, 
on the same nitrogen intake would appear to support the theory 
that some toxogenic influence had been removed. To this influence, 
however, must be added as a cause of retention the higher level 
of reparative processes going on in the body; as, for example, in 
the bone marrow and possibly other organs. It is, ho%vever, difiS- 
cult to reconcile our slight positive balance with Umber's marked 
negative balance, before operation. 

The casei? to whidi Pearce refers, a,s exhibiting a positive 
nitrogen balance, are one of congenital hemolytic icterus (8) 
and one of pernicious anemia (9). In neither instance wa^; 
there more than a slight positive nitrogen balance before splen- 
ectomy and in the case of pernicious anemia, some time after 
the operation, there was no increased assimilation of nitrogen. 
Both cases were studied for short periods only. It may be 
concluded, therefore, that a markedly positive nitrogen bal- 
ance has not as yet been observed in pernicious anemia. 

The following cases of pernicious anemia were put on liigli 
diets. The food was made as appetizing as possible, the per- 
sonal wishes of the patients were consulted and no attempt was 
maxle to maintain a definite proportion of proteins, fats or 
carbohydrates. It is notoriously difficult to administer large 
quantities of food to many cases of pernicious anemia. This 
problem was encountered only with H. M., Medical No. 37187. 
However, careful nursing and attention to a moderate degree 
of myocardial insufficiency finally won the day and this man 
consumed a fair amount of food, though never with the same 
relish as the other cases. It is not intended to convey the 
imjaression that it has been possible to force feeding in every 
patient. In fact, G. R. B., Medical No. 36704, after doing 
.splendidly for some time following his discharge from the 
hospital, threw all precautions to the winds, stopped his hydro- 
chloric acid, indulged in a great deal of alcohol, and finally 
returned for treatment. After one month's attempt, under 
ideal conilitions. and with the f)atient's enthusiastic co-o))era- 
tiun, it was rmuiil impossible to administer a high diet. 

These patients were all kept under .strict supervision in a 
small metabolism ward. They remained in bed, thus estab- 
lishing their metabolic requirements at as low a level as possi- 
iilc. The only medication which they received was dilute 
hydrochloric acid. In one case transfusions were given. The 
food values were calculated according to Atwater and Bryant's 
tables. An actual analysis of a considerable number of .samples 
showed that such calculations were accurate for the food 
materials used. The nitrogen of the urine and feces was 
determined by the Ivjeldahl method. 

The histories and results of obscrvati<iiis in these cases arc 
as follows: 

G. R. B. Medical No. 36704. Male, white, aged 50. 
Diagnosis: Pernicious anemia. 

Admitted to The Johns Hopkins Hospital October 2, 1916. 
The patient lived in Mississippi up to five years ago, and during 
that time had chills and fever every year. He complains of weak- 



ness and shortness of breath on exertion. He has had numbing 
and tingling in the legs occasionally, and has noted that his skin 
has been somewhat yellow. 

On admission, he was well developed and nourished but ex- 
tremely pale. The sclerse had a lemon yellow color. The area 
of precordial dulness measured 4 x 12 cm. There was a blowing 
systolic murmur over the entire precordium. The liver was felt 
one finger's breadth below the costal margin; the spleen was not 
felt. Otherwise, the physical examination was negative. 

On October 3, the red blood cells were 1,216,000. the hemoglobin 
28 per cent., the white blood cells 5200, and the differential count 
was as follows: Polymorphonuclear neutrophiles 64 per cent, lym- 
phocytes 16 per cent, large mononuclear cells 7 per cent, eosino- 
philes 3 per cent, basophiles 1 per cent, myelocytes 3 per cent, tran- 
sitionals 3 per cent, and unclassified cells 3 per cent. The blood 
smear showed a moderate variation in size and shape of the red 
blood cells, with a tendency towards the large type of red blood 
cell. The red cells were deeply and diffusely stained and no 
nucleated red cells were seen; there was a slight degree of baso- 
philia, but no granular degeneration. The blood platelets appeared 
to be decreased. 

On October 15, thirteen days after admission, after two trans- 
fusions had been given, and the red cells had increased to almost 
2,000,000, the forced feeding was begun. The further course of 
events may be followed in Table 1. During this period he received 
two additional transfusions, as indicated on the chart, and was 
taking 20 to 40 minims of dilute hydrochloric acid after meals. 
No other medication, except an occasional cathartic, was given. 
The patient was kept in bed while these observations were made. 

H. M. Medical No. 377S7. Male, white, aged 60. 

Diagnosis: Pernicious anemia. 

Admitted to The Johns Hopkins Hospital April 14, 1917. 

In March, 1915, following an " attack of grippe," he was short 
of breath and weak. In the spring of 1916, his skin began to burn, 
itch and tingle. He was very hypersensitive to odors, but nothing 
abnormal could be found in his nose by specialists. His eyes be- 
came weaker and black dots impaired his vision. This condition 
became worse until at present he can scarcely read more than 15 
minutes at a time. In April, 1916, shortness of breath, paleness, 
jaundice and weakness became so marked that he went to the 
Bermuda Islands to recover, but obtained no relief. In the winter 
of 1916-17, he was so weak and short of breath that he could 
scarcely walk. He went to Florida and his symptoms cleared 
up to a remarkable degree. Later, he again relapsed and he came 
to the hospital for treatment. His appetite is very poor and his 
bowels are constipated. 

The patient was extremely pale. There was marked dyspnea 
even on slight exertion. The skin and sclera had a lemon yellow 
color. He was well nourished. There were numerous fresh and old 
hemorrhages scattered throughout both retinas. The area of 
precordial dulness extended 3 cm. to the right and 12 to the left. 
At the apex there was a soft blowing systolic murmur. The second 
pulmonic sound was louder than the aortic second. The i)ulse was 
regular in force and frequency. The rate varied from SO to 95. The 
blood pressure was 110 systolic and 60 diastolic. The liver edge 
was at the costal margin; the spleen was felt one finger's breadth 
below the costal margin; it appeared to be soft. On April 19 the 
red blood cells were 1,000,000, the hemoglobin 25 per cent, and the 
white blood colls 4C00. On May 5 the differential count showed 
55.6 per cent polymorphonuclear cells, 35.2 per cent lymphocytes, 
5.2 per cent large mononuclear cells, 2 per cent transitionals, 1.6 
per cent eosinophiles, and 0.4 per cent basophiles. The blood smear 
on April 18 showed great variation in the size and shape of the 
red cells; there were many microcytes and macrocytes; the red 
blood cells were of a dark color and diffusely stained; there was 
a moderate number of normoblasts and megaloblasts; there was 



June, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



131 





TABLE 


1.— RESULTS OP FORCED FEEDING IN A CASE OF 


PERNICIOUS ANEMIA (G. R 


B., MED. NO. 36704) 




Food 




Nitrogen per 


day, gm. 




Blood 


Transfusion 

citrated, 
blood, c.c. 




Date 


Protein, 
gm. 


Fat, 


Carbo- 
hydrate, 
gm. 


Total 
calories 


Calories 
per kilo 
per day 


Urine 


Feces 


Total 
output 


Intake 


Balance 


Red blood cells 
per c. mm. 


Hemoglobin 
per cent 


Weight, 
kg- 


10-15-16 


89.5 
106.1 
103.2 
114.5 

95.9 
100.1 
112.9 
118.0 
117.8 

99.1 

69.4 
116.8 
116.3 
106.1 
100.8 
117.2 

77.7 

85.2 
123.8 
129.5 

97.6 

90.7 
111.2 

93.8 
122.2 
103.7 
124.0 

99.4 


128.4 
159.6 
184.1 
133.5 
183.5 
139.9 
201.6 
177.3 
172.8 
132.3 
86.9 
161.8 
202.0 
200.3 
160. 1 
160.3 
127.1 
149.6 
165.2 
180.0 
183.9 
121.2 
157.5 
150.1 
164 . 9 
160.4 
220.9 
139.1 


289.9 
276.7 
326.6 
353.2 
324.4 
306.3 
.301.1 
411.0 
391.0 
273.2 
174.0 
.377.1 
371.8 
430.3 
505.3 
498.3 
402.9 
295.9 
500.0 
518.8 
300.0 
442.9 
272.4 
501.6 
307.8 
544.3 
504.1 
469.2 


2750 
3034 
3474 
3159 
3430 
2967 
3572 
.3818 
3693 
2757 
1806 
3130 
3880 
4063 
3974 
4014 
3152 
2954 
4094 
4332 
4160 
3315 
3038 
3837 
4117 
4149 
4630 
3625 


39.1 
43.3 
49.4 
44.8 
48.5 
42.1 
50.7 
54.0 
51.6 
38.9 
25.4 
50.7 
54.9 
57.6 
56.2 
56.2 
43.9 
41.1 
37.5 
61.0 
58.3 
46.2 
42.4 
54.0 
57.8 
57.6 
63.5 
49.8 


10.69 
8.45 
8.53 
9.89 
10.92 
7.17 
12.43 
9.27 
13.44 
13.99 
7.55 
12.80 
12.15 
10.43 
9.27 
10.35 
8.95 
11.34 
11.99 
9.14 
11.93 
9.59 
13.57 
11.03 
10.52 
9.90 
6.82 
10.16 


3.18 

3.00* 

3.00* 

3.00* 

2.13 

2.13 

4.24 

3.79 

3.02 

3.02 

1.61 

1.61 

1.61 

2.98 

2.98 

5.22 

2,17 

2.17 

2.17 

3 45 

3.45 

3.45 

3.45 

3.40 

3.40 

3.40 

3.45 

3.45 


13.87 
11.45 
11.53 
12.89 
13.05 

9.30 
16.67 
13.06 
10.46 
17.01 

9.16 
14.41 
13.76 
13.41 
12.25 
15.. 57 
11.12 
13.51 
14.16 
12.59 
15.38 
13.04 
17.02 
14,43 
13.92 
13.30 
10.27 
13.61 


14.3 
10.9 
16.5 
18.3 
15.3 
16.0 
18.1 
18.9 
18.8 
15.9 
11.1 
18.7 
18.6 
17.0 
16.1 
18.8 
12.4 
13.6 
19.8 
20.7 
15.6 
14.5 
17.8 
14.9 
19.fi 
16.0 
19.8 
15.9 


+ .43 

+5.45 
+ 4.97 
+5.41 
+2.25 
+6.70 
+ 1.43 
+5 . 84 
+2.34 
—1.11 
+ 1.94 
+4.27 
+4.84 
+3.59 
+ 3.85 
+3.23 
+ 1.28 
+ .09 
+5.64 
+8.11 
+ .22 
+ 1.46 
+ .78 
+ .47 
+5.68 
+3.30 
+9.53 
+2.29 




36 

36 

36 
39 

39 
40 

45 

48 


506 
500 


70.3 
70.4 
70.2 
70.4 
70.6 
70.4 


10-16-16 
10-17-16 


2,016,000 


10-18-16 




10-19-16 




10-20-16 
10-21-16 


1,710,000 


10-22-16 




70 6 


10-23-16 




71 3 


10-24-16 
10-25-16 
10-26-16 


1,848,000 
2,248,000 


70.7 
70.9 
69 6 


10-27-16 




70 6 


10-28-16 




70 5 


10-29-16 




70 7 


10-30-16 




71 3 


10-31-16 
11- 1-16 
11- 2-16 


2,328,000 
2,368,000 


71.7 
71.5 
71 1 


11- 3-16 




71 


11- 4-16 




71.3 


11- 5-16 
11- 6-16 
U- 7-16 


3 ; 224', 000 


71.7 
71.5 
71.0 


11- 8-16 




71.2 


11- 9-16 




71.9 


11-10-16 




72 8 


11-11-16 


2,760,000 


72.8 



*The nitrogen contenit of the feces was estimated on the 



; the remaining: figures represent actual determinations 



TABLE 2.— RESULTS OF FORCED FEEDING IN A CASE OF PERNICIOUS ANEMIA (H. M., MED. NO. 37787) 



Carbo- 
hydrate, 
gm. 



Calories 
per kilo 
per day 



Nitrogen per day, gm. 



Urine 


Feces 


7.74 


2.00 


6.11 


2.00 


5.28 


2.00 


7.06 


2.00 


5.44 


1.80 


Lost 


1.80 


8.03 


1.80 


7.39 


1.80 


8,20 


1.80 


6.57 


1.80 


7.44 


1.72 


8.58 


1.72 


8.00 


1.72 


9.04 


1.72 


9.41 


1.72 


10.98 


2.06 


10.98 


2.00 


11.13 


2.06 


9.65 


2.06 


10.44 


2.06 


10.07 


2.06 


13.25 


2.13 


13.17 


2.13 


13.32 


2.13 


13.07 


2.13 


13.46 


2.07 


14.95 


2.07 


15.20 


2.07 


10.56 


2.07 


13.16 


2.07 


15.62 


2.07 


14.47 


2.07 



Total 
output 



Intake Balance 



Red blood cells Hemoglobin, 
per c. mm. per cent 



4-18-17 
4-19-17 
4-20-17 
4-21-17 
4-22-17 
4-23-17 
4-24-17 
4-25-17 
4-26-17 
4-27-17 
4-28-17 
4-29-17 
4-30-17 
5- 1-17 
5- 2-17 
.5- 3-17 
5- 4-17 
5- 5-17 
5- 6-17 
.5- 7-17 
5- 8-17 
3- 9-17 
5-10-17 
5-11-17 
5-12-17 
5-13-17 
5-14-17 
5-15-17 
5-10-17 
5-17-17 
5-18-17 
5-19-17 



52.2 
50.9 
79.3 
68.1 
83.0 
101.5 
88.8 
119.3 
111.3 
113.3 
119.3 
122.8 
1.30.9 
115.4 
137.3 
123.0 
134.0 
140.9 
123.5 
143.0 
1.53.3 
146.3 
157.4 
151.8 
128.3 
140.7 
152.6 
156.9 
168.7 
151.2 
1.53.6 
166.0 



84.0 
87.0 
173.6 
137.8 
177.7 
225.6 
216.8 
224.7 
244.4 
251.5 
245.6 
236.3 
234.1 
253.5 
247.6 
226.4 
256.9 
250.8 
257.9 
257.9 
21)3 . 1 
261.6 
270.3 
261.4 
245.1 
249.2 
2.56.7 
258.2 
292.3 
285.6 
266.7 
263.3 



193.8 
144.3 
258.9 
336.8 
287.6 
267.2 
339.0 
321.8 
355.8 
362.3 
334.1 
368.1 
372.4 
357 . 
309.5 
355.5 
317.7 
382.1 
381.9 
348.8 
404.9 
361.6 
382.9 
421.9 
391.5 
366.4 
421.8 
353.9 
337.1 
376.0 
426.3 
373.1 



13.9 
18.5 
27.6 
13.9 
13.9 
13.9 
13.9 
13.9 
13.9 
13.9 
13.9 
13.9 
13.9 
13.9 
13.9 
13.9 
13.9 
13.9 
13.9 
13.9 



1790 
1610 
3097 
3072 
3365 
3706 
3867 
3995 
4285 
4386 
4240 
4307 
4338 
4392 
4232 
4165 
4338 
4374 
4367 
4311 
4833 
4613 
4729 
4783 
4410 
4421 
4742 
4493 
4792 
4818 
4858 
4660 



26.6 
23.8 
45.6 
44.7 
48.4 
53.4 
54.9 
56.6 
60.7 
61.8 
59,3 
60.6 
61.4 
62.3 
60.4 
59.3 
61.4 
64.7 
64.4 
63.6 
68.2 
64.9 
66.6 
66.7 
61.6 
61.6 
66.0 
62.2 
66.3 
67.0 
66.8 
64.1 



9.74 
8.11 
7.28 
9.06 
7.24 



8.35 
8.14 
12.68 
10.89 
13.28 



1.80+116.24 
9.83 14.20 



9.19 
10.00 

8., 37 

9.16 
10.30 

9.72 
10.76 
11.13 
13.04 
13.04 
13.19 
11.71 
12.50 
12.73 
13.38 
13.30 
15.45 
15.20 
15.53 
17.02 
17.27 
18.03 
15.23 
17.69 
16.54 



19.07 
17.80 
18.12 
19.08 
19.64 
20.94 
18.46 
21.96 
19.68 
21.44 
22.54 
19.76 
22.88 
24.56 
23.40 
25.18 
24.28 
20.. 52 
23.47 
24.41 
25.10 
26.99 
24.19 
24.57 
25.56 



— 1.39 
+ 0.03 
+ 5.40 
+ 1.83 
+ 6.04 
+ 14.44 
+ 4.40 
+ 9.88 
+ 7.80 
+ 9.75 
+ 8.92 
+ 9.34 
+ 11.22 
+ 7.70 
+10.83 
+ 6.64 
+ 8.40 
+ 9.35 
+ 8.05 
+ 10.38 
+ 11.83 
+ 6.02 
+ 9.88 



+ 8.36 
+ 8.96 
+ 6.88 
+ 10.02 



1,000,000 
i, 476, 000 

i,56-ii666 

2,356,666 
2,308,000 
2,224,666 
2,676,660 
3 j 068, 606 
2,954,066 
2,976,660 

3,240,666 
3,016,600 
3,376,666 
3,728,666 



67.2 
67.6 
67.8 
68.7 
69.5 
69.4 
70.3 
70.6 
70.5 
70.9 
71.5 
71.0 
70.6 
70.4 
70. L 
70.2 
70.5 
70.0 
70.8 
70.9 
70.8 
71.0 
70.9 
71.7 
71.5 
71.7 
71.8 
72.1 
72.2 
71.8 
72.7 
72.7 



132 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 328 



granular degeneration and basophilia, and the blood platelets were 
diminished. 

The patient's symptoms were evidently caused by anemia and 
insufficient heart action. The only medication which he received 
was infusion of digitalis and dilute hydrochloric acid. With these 
aids liis dyspnea was diminished and his appetite increased. The 
diet, the red blood cell counts and the percentage of hemoglobin 
may be followed in Table 2. His diet was forced as much as pos- 
sible from April IS until May 20. During this period he remained 
in bed. On May 20 he felt so well, the dyspnea, weakness and 
dimness of vision having disappeared completely, that he insisted 
on leaving the hospital. 

W. B. Medical No. 36933. Male, white, aged 63. 

Diagnosis: Pernicious anemia; lobar pneumonia. 

Admitted to The Johns Hopkins Hospital September 21, 1916. 

The patient was well until two days prior to his admission to the 
hospital. At this time he had a chill and complained of pain 
in the back. He was admitted to the hospital in an almost stupor- 
ous condition and was difficult to arouse. He had been working 
as sexton in a church until he was taken sick and had been doing 
fairly hard work. 

The patient had the signs and symptoms of a lobar pneumonia 
in the right lower lobe. These cleared up shortly, so that six days 
after admission the temperature was normal and all traces of the 
acute disease had disappeared. The physical examination exclu- 
sive of the signs that could be referred to the pneumonia showed 
that the patient was fairly nourished but was very pale. There 
was slight edema above the ankles. The scleras had a lemon tint; 
there were numerous small hemorrhagic spots upon the retins. 
Over the whole precordium there was a blowing systolic murmur 
which was not transmitted to the left beyond the apex region. The 
spleen was not felt; the liver was two fingers' breadth below the 
costal margin. Otherwise the physical examination was negative. 
On September 21, the red blood cells were 656,000, the hemo- 
globin was 15 per cent, and the white blood cells 3500. The 
differential count showed that the polymorphonuclear neutrophiles 
were 60 per cent, the lymphocytes 34.5 per cent, the large mononu- 
clears 3.5 per cent, the transitionals 1.5 per cent, and the baso- 
philes 0.5 per cent. The cells varied very much in size and shape; 
very many were distinctly larger than normal. There was baso- 
philic and granular degeneration. A few megaloblasts and normo- 
blasts were present. 

The patient was transfused twice and given two courses of 
sodium cacodylate. On November 17, his red blood cells had risen 
to 3,500,000, and his hemoglobin to 70 per cent. This was almost 
exactly two months after his admission to the hospital. At that 
time, forced feeding was begun, the results of which are given in 
Table 3. During the period of high diet, he was given 20 minims of 
dilute hydrochloric acid after meals, but no other medication, and 
was kept in bed. 

S. F. Medical History No. 37840. Male, while, a,ged 38. 

Diagnosis: Chronic myeloid leukemia, secondary anemia. 

Admitted to The Johns Hopkins Hospital December 17, 1916. 

Seven years ago the patient first noticed that his abdomen was 
increasing in size. He was treated in the University Hospital of 
Baltimore one year later with X-rays, the diagnosis being spleno- 
myelogenous leukemia. As the result of this therapy the spleen 
became very much smaller. Two years later he began to take 
arsenic, whlcli he continued up to one year ago. The tumor in the 
abdomen has progressively increased in size; there have been fre- 
quent nosebleeds. The patient bleeds easily and a small injury will 
cause a bruise. On November 19, 1916, the patient went to 
Dr. Kelly's sanatorium, where he took tliree treatments of radium 
about 8 to 10 days apart. Under this therapy his spleen shrank 
markedly and he felt stronger than before. After an interval of 
three weeks, his gums became swollen and began to bleed. Ten 



days ago, epistaxis began and he bled for four days and four 
nights, losing a great deal of blood. At about the same time, small 
hemorrhages appeared in the skin. These would soon disappear 
and be replaced by a new crop. 

The patient was well nourished. There was no dyspnea. He was 
constantly expectorating blood and blood was oozing from the 
nostrils and the gums. There were numerous hemorrhages in the 
skin. These were especially marked in the lower extremities. 
The largest ones were in the back, being 10 x 5 cm. The skin and 
sclerae had a peculiar orange tint. The heart and lungs showed 
nothing of note. The liver edge was felt at the costal margin; the 
spleen was remarkably enlarged, extending to about the level of 
the crest of the ilium below and almost to the median line on the 
right. The red blood cells were 3,120,000; the white blood cells 
4600; the hemoglobin 30 per cent. The differential count showed 
polymorphonuclear cells 74.8 per cent, small mononuclear cells 
16 per cent, large mononuclear cells 6.8 per cent, transitional cells 
0.4 per cent, myelocytes O.S per cent, eosinophiles 0.4 per cent, and 
basophiles O.S per cent. Before radiation the blood count had been: 
Red blood cells 2,984,000; white blood cells 160,000; hemoglobin 
52 per cent; and the differential count: Polymorphonuclear neu- 
trophiles 20.7 per cent, small mononuclear cells 10.0 per cent, 
large mononuclear cells 2.3 per cent, transitional cells 1.6 per cent, 
myelocytes 5.5 per cent, basophiles 3.3 per cent, and eosinophiles 
3.6 per cent. 

From December 17 to March 2 numerous transfusions were given, 
and arsenic therapy was employed. There was no improvement: 
the bleeding from the nasopharynx, which continued during this 
period, finally resulting in a very severe secondary anemia. The 
blood platelet count was very low; the blood clot did not contract 
but was typical of a clot deficient in blood platelets. A marked 
leucopenia accompanied this secondary anemia. There were 
several retinal hemorrhages and marked bleeding from the gums. 
Hemorrhages into skin were present to only a very slight degree. 
On March 2 the red blood cell count was 912,000, the hemoglobin 
20 per cent and the white blood cells 1350. On this date forced feed- 
ing was begun, the hemorrhages ceased, and the further course of 
the patient can be followed in Table 4. 

It is vei\y evident from the study of the figures as given in 
Tables 1, 2 and 3, that there was no difficulty encountered at 
any time during the observation in bringing about an exten- 
sive assimilation of nitrogen. In the case of G. E. B., Table ], 
the only patient in whom transfusions were employed, it may 
be noted that following each of the transfusions there was a 
lowered nitrogen balance. This was only to be expected, inas- 
much as the nitrogen contained in the transfused blood was 
not included in the intake. This result would indicate that 
much of the protein material contained in the blood intro- 
duced intravenously was lost in the urine. The positive nitro- 
gen balance diminished considerably a few days after the sec- 
ond transfusion. The patient did not consume as mucli food 
on some of these days, and it is very difficult to ascertain the 
exact reasons for these fluctuations. The other two cases, who 
were not transfused (Tables 2 and 3) certainly exhibited a 
much steadier positive nitrogen balance. The amount of nitro- 
gen and the caloric value of the diet may possibly be most 
readily appreciated from the summary given in Table 5. One 
of these patients retained 3.4 gms. of nitrogen a day for 28 
days, another, 3.4 gms. a day for 32, and the third 6.8 gms. 
a day for 36 days. These are very large positive balances, and 
there can be no doubt that cases of pernicious anemia can 
assimilate nitrogen readily if put upon forced diets. 



JUN'E, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



133 



TABLE 3.— RESULTS OF FORCED FEEDING IN A CASE OF PERNICIOUS ANEMIA (W. B., MED. NO. 36933) 



Carbo- 
hydrate, 
gm. 



Calories 
per kilo 
per day 



Nitrogen per day, gni. 



Total 
output 



Red blood cells Hemoglobin 
per c. mm. per cent 



11-lG-lt) 
11-17-10 
11-18-lG 
11-19-lG 
ll-20-l(i 
11-21-16 
11-22-16 
11-23-10 
11-24-10 
11-25-16 
11-26-10 
11-27-16 
11-28-16 
11-29-16 
11-30-16 
12- 1-16 
12- 2-16 
12- 3-16 
12- 4-16 
12- 5-16 
12- 6-16 
12- 7-16 
12- 8-10 
12- 9-16 
12-10-16 
12-11-16 
12-12-16 
12-13-16 
12-14-16 
12-15-16 
12-16-10 
12-17-10 
12-18-10 
12-19-16 
12-20-16 
12-21-16 



79.9 
80.2 
79.9 
80.2 
79.0 
80.2 
80.2 
81.4 
81.2 
80.2 
80.5 
80.2 
80.5 
80.6 
80.2 
79.8 
80.4 
80.2 
80.0 
80.2 
89.2 
80.1 
80.3 
80.1 
80.2 
80.7 
80.2 
91.3 
80.6 
80.0 
145.9 
80.0 
80.3 
80.0 
80.1 
80.0 



125.0 
125.2 
125.7 
124.0 
126.8 
123.9 
126.5 
124.9 
125.1 
125.2 
125.7 
125.0 
125.5 
124.9 
125.0 
125.1 
125.8 
125.2 
125.0 
124.9 
103.3 
124.9 
125.6 
125.4 
125.2 
125.5 
125.6 
95.4 
125.0 
125.4 
135.1 
125.8 
125.5 
125.5 
124.9 
125.8 



230.1 
229.0 
230.1 
230.5 
400.2 
400.2 
400.1 
399.9 
401.7 
400.6 
401.8 
402 . 1 
401.1 
400.7 
402.1 
400.0 
400.9 
400 . 6 
400.8 
4',11.2 
251.5 
400.3 
400.6 
400.8 
400.6 
400.7 
400.1 
274.1 
400.2 
400.4 
273.4 
400.0 
400.4 
400.0 
400.3 
400.0 



2434 
2432 
2440 
2427 
3144 
3122 
3145 
3136 
3143 
3135 
3140 
3141 
3142 
3135 
3141 
3130 
3144 
3135 
3136 
3136 
2358 
3131 
3139 
3137 
3135 
3141 
3137 
2385 
3134 
3136 
2975 
3138 
3138 
3135 
3131 
3138 



48.9 
49.6 
49.7 
49.8 
63.6 
62.4 
62.2 
61.0 
01.7 
61.4 
61.2 
60.7 
60.3 
59.9 
59.6 
59.3 
59.2 
58.4 
58.5 
58.1 
43.8 
59.2 
58.4 
57.7 
58.2 
57.4 
57.2 
43.3 
57.6 
57.0 
54.0 
57.7 
57.2 
56.5 
50.3 
55.9 



10.49 
10.00 
8.21 
11.32 
10.56 
8.93 
8.57 
7.84 
7.76 
5.60 
5.94 
6.03 
5.06 
4.84 
4.08 
3.74 
2.98 
4.50 
4.51 
5.10 
5.22 
7.08 
6.04 
4.47 
5.28 
5.54 
5.05 
6.00 
4.. 94 
6.21 
7.19 
9.00 
7.13 
6.93 
6.49 
5.43 



0.43 
0.43 
0.42 
l..i8 
1.58 
1.58 
1.58 
1.58 
1.58 
1.58 
1.82 
1.82 
1.82 
1.82 
2.51 
2.51 
2.38 
2.37 
2.37 
2.37 
2.01 
2.61 
2.61 
2.61 
2.80 
2.80 
2.80 
2.80 
2.80 
2.80 
2.80 
2.80 
3.03 
3.03 
3.03 
3.03 



10.92 
10.49 
8.03 
12.90 
12.14 
10.51 
10.15 
9.42 
9.34 
7.18 
7.76 
7.85 
6.88 
6.60 
6.59 
0.25 
5.36 
0.87 
6.88 
7.47 
7.83 
9.69 
8.05 
7.08 
8.08 
8.34 
7.85 
8.80 
7.74 
9.01 
9.99 
11.80 
10.16 
9.96 
9.52 
8.46 



12.78 
12.83 
12.78 
12.83 
12.64 
12.8:J 
12.83 
13.02 
12.99 
12.83 
12.88 
12.83 
12.88 
12.89 
12.83 
12.76 
12 . 86 
12.83 
12.89 
12.83 
14.27 
12.81 
12.84 
12.81 
12.83 
12.91 
12.83 
14.60 
12.89 
12.80 
23.34 
12.80 
12.84 
12.80 
12.81 
12.80 



+ 1 
+ 2 
+ 4, 
— 0. 
+ 0, 
+ 2. 
4- 2, 



+ 3. 

+ 5. 

+ 5. 

+ 4. 

+ 6. 

+ 6. 

+ 6. 

+ 6. 

+ 7. 

+ 5. 

+ 6. 

+ 5. 

+ 6. 

+ 3. 

+ 4. 

+ 5. 

+ 4.75 

+ 4.57 



-1-13 
+ 1. 
+ 2. 
+ 2. 
+ 3. 
+ 4. 



3,500,000 
3,666^660 



4,000,000 



4,503,000 



4,100,000 



4,040,000 



49.7 
49.0 
49.0 
48.7 
49.4 
50.0 
50.5 
50.9 
.50.9 
51.0 
51.4 
51.7 
52.1 
52.3 
52.7 
52.7 
.53.1 
53.6 
53.0 
53.9 
53.8 
52.8 
53.7 
54.3 
53.8 
54.7 
54.8 
55.0 
54.4 
55.0 
55.0 
54.3 
54.8 
55.4 
55.6 
56.1 



TABLE 4.— RESULTS OF FORCED FEEDING IN (S. F., MEDICAL NO. 37840) A CASE OF CHRONIC MYELOGENOUS LEU- 
KEMIA, COMPLICATED BY SECONDARY ANEMIA, BROUGHT ABOUT BY HEMORRHAGES FOLLOWING RADIUM THERAPY 



gm. 



Calories 
per kilo 
per day 



Nitrogen per day, gm. 



Red blood cells Hemoglobin 
per cent 



Weight 
kg. 



3- 3-17 
3- 4-17 
3- 5-17 
3- 0-17 
3- 7-17 
3- 8-17 

3- 9-17 
3-10-17 
3-11-17 
3-12-17 
3-13-17 
3-14-17 
3-15-17 
3-16-17 
3-17-17 
3-18-17 
3-19-17 
3-20-17 
3-21-17 
3-22-17 
3-23-17 
3-24-17 
3-25-17 
3-26-17 
3-27-17 
3-28-17 
3-29-17 
3-30-17 
3-31-17 

4- 1-17 
4- 2-17 
4- 3-17 
4- 4-17 



118.1 
120.5 
134.9 
114.0 
123.1 
125.2 
135.2 
157.5 
85.7 
137.4 
143.5 
140.2 
130.9 
125.5 
1.56.7 
151.7 
145.0 
150.8 
163.0 



162.3 
154.3 
162.8 
147.1 
105.9 
102.9 
100.9 
1.50.0 
1.57.6 
175.6 
161.5 
177.3 
90.8 
149.0 



165.8 
159.7 
176.1 
160.6 
159.1 
155.3 
184.2 
174.9 
96.4 
181.3 
176.6 
174.0 
189.0 
172.5 
208.0 
189.8 
195.0 
194.8 
200.8 
194.0 
212.7 
214.8 
170.9 
215.4 
211.0 
201.1 
217.8 
208.8 
179.4 
201.9 
180.4 
100.8 
203.9 



372.8 
319.4 
375.2 
399.1 
389.1 
402 . 4 
414.0 
411.0 
298.2 
427.6 
431.7 
440.9 
410.0 
459 . 7 
409.8 
515.5 
510.0 
505.0 
405 . (i 
514.4 
461.3 
447.6 
549.7 
446.7 
450.5 
4S0.8 
484.4 
405.8 
515.5 
478.4 
518.0 
204.8 
484.3 



3554 
3289 
3729 
3599 
3580 
3007 
3904 
3961 
2471 
4002 
4001 
4001 
4002 
4004 
4503 
4501 
4502 
4501 
4500 
4579 
4.)02 
4500 
4502 
4515 
4502 
4501 
4029 
4498 
4502 
4.501 
4528 
2395 
4493 



59.6 
55.1 
62.5 
60.3 
00.0 
60.5 
59.9 
59.9 
37.3 

62.7 
61.9 
61.9 
62.0 
69.3 
68.6 
68.6 
68.4 
68.2 
09.0 
67.5 
67.3 
67.2 
67.3 
60 . 9 
66.8 
68.1 
66.3 
66.0 
65.8 
00.1 
34.0 
66.2 



12.17 
13.12 
14.10 
10.29 
13.32 
10.11 
13.79 
11.10 

9. SO 
11.90 
13.02 

9.73 
10.50 

4..>9 
12.27 
11.28 
11.94 
12.64 
12.47 
11.38 
12.24 
13.20 
11.71 
13.75 
14.50 
14.44 
12.90 
15.31 
15.48 
13.95 
12.13 
12.88 



3.23 
3.23 
3.23 
3.23 
3.23 
3.23 
1.97 
1.97 
1.97 
1.97 
1.97 
2.46 
2.46 
2.46 
2.46 
2.40 
2.46 
2.25 
2.25 
2.25 
2.25 
2.25 
2.25 
2.25 
3.17 
3.17 
3.17 
3.17 
1.59 
1.59 
1.59 
1.59 
1.59 



15.40 
16.35 
17.33 
13.52 
16.55 
12.08 
15.76 
13.07 
11.77 
13.87 
16.08 
12.19 
12.96 
7.05 
14.73 
13.74 
14.19 
14.89 
14.72 
13.63 
14.49 
15.45 
13.96 
16.92 
17.73 
17.61 
16.13 
16.90 
17.07 
15.54 
13.72 
14.47 



18.89 
19.28 
21.58 
18.33 
19.69 
20.03 
21.03 
25.20 
13.71 
21.98 
22.96 
22.43 
20.94 
20.08 
25.07 
24.27 
23.20 
24.12 
26.08 
25.96 
24.08 
26.04 
23.. 53 
26.54 
20.00 
25.74 
24.09 
25.21 
28.09 
25.84 
28.30 
14.52 
23.84 



-f 3.88 
4- 5.23 
+ 1.00 
+ 0.17 
+ 3.48 
-I- 9.55 
+ 9.44 
-I- 0.04 
+ 10.21 
+ 9.09 
4-0.35 
-I- 8.75 
+ 7.12 
-1-18.02 
+ 9.54 
+ 9.46 
+ 9.93 
+ 11.19 
+ 11.24 
+ 11.05 
+ 11.55 
+ 8.08 
+ 12.58 
+ 9.14 
+ 8.01 
+ 6.48 
+ 9.08 
+ 11.19 
+ 8.77 
+ 12.82 
+ 0.80 
+ 9.37 



912,000 
1,152,000 
1,536,000 

i, 392, 666 
1,172,000 
1.444,000 
1,842.000 
1,572,000 
1,004,000 
1,-584,000 
1,688,000 
1,840,000 

i] 8.56, 666 
1,780,000 

1^984,666 
1,904,000 
2,128,000 



1,984,000 


38 


2,204,000 


38 


2,400,000 


40 


2.368.000 


45 


2.408,000 


48 


2.356.000 


48 


2,516,000 


51 


2,892,000 


32 



2,788,000 
3,056,000 



63.7 
64.6 
64.6 
04.5 
04.9 
65.6 
65.6 
05.8 
60.0 
06.3 
60.6 
66. S 
66.9 
67.0 
67.2 
67.3 
67.9 
07.8 
68.2 
68.4 
68.6 
69.1 



134 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 328 



It is extremely hazardous to draw conclusions from such a 
small number of cases in regard to the effect of the diet on the 
hemoglobin and red cells. The tendency to remissions which 
cases of pernicious anemia constantly manifest makes it impos- 
sible to say definitely what role the diet played in influencing 
the blood picture. In two of the cases the improvement was 
not very striking; the hemoglobin rose from 36 to 48 per cent 
in G. E. B. in 28 days (Tables 1 and 5) ; during that time the 
patient received two transfusions; in W. B. the hemoglobin 
and red blood cells were only very slightly increased at the 
end of 36 days (Tables 3 and 5); in H. M., on the other 
hand, there was a very marked improvement, the hemoglobin 
rising from 25 to 60 per cent in 32 days and the red blood cells 
increasing correspondingly (Tables 2 and 5). 

There is no doubt that the nitrogen in these eases is 
retained. The question as to what use the body makes of it 



Conclusions. — By means of a forced diet a positive nitrogen 
balance may be readily obtained in pernicious anemia. Of 
the three cases observed, there was an improvement in the 
blood picture in each instance. The latter result must be 
regarded as suggestive only, inasmuch as too few patients have 
been studied to warrant a definite general conclusion. 

Acknowledgment is due to Miss Susie McFarlane for 
organizing the Metabolism Ward in which these patients were 
studied, and for carrying out these difficult feeding experi- 
ments in a most efficient manner. 



LITERATURE 
1. Pearce, R. M., Krumbhaar, E. B., and Frazier, C. H.: 
Spleen and Anjemia," 1918, p. 231. 



TABLE 5.— SUMMARY OP RESULTS (TABLES 1, 2, 3 AND 4) OF FORCED FEEDING IN THREE CASES OF PERNICIOUS AND 

ONE OP SECONDARY ANEMIA 



Patient 


Period, 
days 


Food per day 


Nitrogen per day, gm. 


Hemoglobin 
during period 
of observation. 


Red blood cells, during 
period of observation 


Protein, 
gm. 


Fat, 
gm. 


Carbo- 
hydrate, 
gm. 


Total 
calories 


Calories 
per kilo 
per day 


Output 
Intake (Urine and Balance 
Feces) 


First 


Last 


First 


Last 


G.R.B.,* Pernicious Anemia. 
H. M., Pernicious Anemia. 
W. B., Pernicious Anemia. 
S. F., Secondary Anemia. 


28 
32 
30 
33 


10.5 
125 
S3 
144 


101 
234 
124 
183 


395 
344 
371 

442 


3547 
4099 
3015 
4105 


50.5 
61.0 
00.7 
68.9 


16.8*, 13.4 1 +3.4 
20.0 j 10.0 +3.4 
13.3 O.,"") +6.8 
23.0 14.3 . +8.7 


36 
25 
70 
20 


48* 
60 

55 


2,016,000 

1,000,000 

3,500,000 

912,000 


2,700.000* 
3,728,000 
4,040,000 
3,056,000 



"This patient r.eceivt-d two transfusions during the period of observ 
nitrogen balance is more favorable in this case than appears in the table ; 
forced diet. 



The nitrogen contained in the transfused blood is not included in the intake ; therefore, the 
rease in the Hb. and the R. B. C. must be considered to be due to the transfusions as well as to 



is another matter. Is it permanently assimilated or would it 
be excreted if the observations were continued long enough ? 
Is it useful to the body in regenerating blood cells ? What pro- 
portions of carbohydrate fat and protein will yield the host 
results ? These and a host of other queries are naturally sug- 
gested by the cases reported above and it is obvious that the 
answers must be brought by more extensive experiments. 

A control case of secondary anemia (Tables 4 and 5) was 
treated in the same manner as the patients with pernicious 
anemia, with the exception that no hydrochloric acid was given. 
This individual received a higher caloric diet than the 
other cases. His desire for food was enormous and even with 
an intake of 68.9 calorics per kilo, he claimed that he could 
easily manage a little more. The nitrogen assimilation in this 
patient was decidedly higher than in those with pernicious 
anemia. This may have been accidental, but it suggests that 
the element of protein destruction does play a considerable 
role in pernicious anemia. The gain in hemoglobin and red 
blood cells was almost identical with tliat seen in 11. JI. 
(Tables 2 and 5). 



2. Umber, P.: Zur Pathologie der Bantischen Milzkrankheit, 
Mvinch. med. Woch., 1912, LIX, 1478; also Zur Pathogenese d. 
" Bantisch,en Krankhelt," mit besondere Bertickslclitigung d. 
Stoffumsatzes vor u. nach der Splenectomie. Zeltschr. f. klin. Med. 
1904, LV, 289. 

3. Minot, G. R.: Nitrogen Metabolism Before and After Splenec- 
tomy in a Case of Pernicious Anemia. Bull. Johns Hopkins Hos- 
pital, 1914, XXV, 338. 

4. McKelvy, J. P., and Rosenbloom, J.: Metabolism Study of a 
Case of Congenital Hemolytic Jaundice with Splenomegaly. Arch. 
Int. Med., 1915, XV, 227. 

5. Rosenqvist, E.: Ueber den Eiweisstoffwechsel bei der per- 
niciosen Anamie, mit specieller Beriicksichtigung der Bothrio- 
cephalus Anamie. Ztschr. f. klin. Med., 1903, XLIX, 193. 

6. Umber, F. : Loc. cit. 

7. Von Noorden, C: Metabolism and Practical Medicine, II, 360. 

8. Goldschmidt, S., Pepper, O. H. P., and Pearce, H. M.: Metab- 
olism Studies Before and After Splenectomy in Congenital Hemo- 
lytic Icterus. Arch. Int. Med., 1915, XVI, 437. 

9. Pepper, O. H. P., and Austin, H. J.: Metabolism Studies 
Before and After Splenectomy in a Case of Pernicious Anemia. 
Arch. Int. Med., 1916, XVIU, 131. 



June, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



135 



THE CLINICAL SIGNIFICANCE OF THE IRREGULAR DISTRIBUTION 
OF VARIOUS CELLS AND PARASITES IN THE BLOOD STREAM 
AND THE PRODUCTION OF ABORTIVE LEUKEMIC CHANGES 
AND OF SPLENOMEGALY IN THE MACACUS RHESUS 

By AxDBEw Watsox Sellaeds and Walter Albert Baetjek 



OUTLINE 

I. Predominance of Biological Rather than Mechanical Laws in 

the Circulation of Various Substances In the 
Blood Stream. 

1. Consideration of normal substances under normal and 

under pathologic conditions. 

2. Behavior of foreign material. 

a. Disappearance of foreign material from the 
peripheral circulation shortly after injection. 

6. Temporary disappearance of leucocytes from the 
circulation after the injection of foreign sub- 
stances. 

c. Irregular distribution of parasites in spontaneous 
infections. 

II. Interpretation of Leucocyte Counts. 

1. Distinction between changes In absolute number and 

changes in distribution in the body. 
a. Occurrence of acute temporary leucocytosis. 
6. Occurrence of acute temporary leucopoenia. 

2. Factors governing the leucocyte count. 

a. Infecting organism. 

6. Location of infection in host. 

c. Severity and stage of infection. 

III. Choice of Site of Infection for the Transmission of Infec- 

tious Diseases. 

1. Disadvantages of intravenous injection. 

a. Dilution of material. 

b. Deleterious action of blood serum and cells. 

c. Removal of microscopic particles by lungs and 

other organs. 
(I. Danger of embolism. 

2. Advisability of concentrating the infecting agent in a 

susceptible area. 

IV. Special Considerations in Regard to Leukemia. 

1. Selection of spleen as site of injection. 

2. Susceptibility and resistance of spleen to infection. 

3. Mechanical advantages. 

4. Clinical advantages. 

5. Production of abortive leuksemic changes in Macacus 

rhesus. 



PART I. GENERAL CONSIDERATIONS. 
Of the many remarkable features connected with the blood 
and its circulation, considerable interest is associated with the 
conditions governing the distribtition in the circulation of the 
normal elements of the blood under natural conditions and also 
of foreign elements upon introduction into the blood stream. 
Even a cursory examination of a few details is sufficient to 
disclose the fact that organized cells and probably substances 
in solution do not circulate according to mechanical laws, but 
that their distribution is governed by biological conditions. 



A simple illustration will make this more explicit. When a 
suspension of nucleated red corpuscles is injected intravenously 
into a rabbit, these cells disappear from the circulation within 
a few minutes instead of becoming equally distributed through 
the blood, as in a mechanical suspension in vitro. In this dis- 
cussion, mechanical laws are contrasted with biological condi- 
tions, but without any intention of opening the question of the 
explanation that is involved. Thus, it is entirely conceivable 
that the biological conditions may rest, in their ultimate analy- 
sis, either upon physical conditions or upon vitalistic phe- 
nomena. 

There is a consideralde amount of data, extending over a 
long period in the literature, in regard to the distribution of 
normal and foreign substances in the blood stream; indeed, 
there are many observations coming often from unexpected 
sources which supply information on this subject. We have 
carried out a few simple experiments to confirm some of the 
essential phenomena which have been reported. The general 
clinical significance of these will be discussed briefly, but 
special attention will be given to the factors bearing upon the 
transmission nf infectious diseases. 

CIRCULATION OF THE NORMAL CONSTITUENTS OF THE BODY 

Even under normal conditions, the cellular elements of the 
blood are not distributed in a purely mechanical way, but are 
subject to variation as the result of changes which are purely 
physiological in their nature. Examples of this are to be found 
in the fluctuations in the number of leucocytes in the peripheral 
blood, such as the leucocytosis of digestion, after cold baths, 
and after exercise. Here it is evident that the increase is due 
essentially not to the withdrawal of fluid from the blood, but to 
an increase in the number of white cells in the peripheral cir- 
culation. The red cell count is also subject to fluctuation. 
Lamson ' lias shown that there is a mechanism for regulating 
the red cell content of the circulating blood, that this mech- 
anism is under nervous control and that it is the liver which 
supplies the body with preformed red cells to meet the acute 
demands. 

There are many types of cells which are ordinarily retained 
completely in the l)one marrow and other blood spaces of the 
body, but after a more or less severe stimulus these cells 
appear in the peripheral circulation. Thus it is a little diffi- 
cult to understand why nucleated red cells are not normally 
abundant in the circulating blood or why a myelocythamia 
develops only after a very considerable stimulus such as the 
severe infections of diphtheria. 



136 



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[Xo. 328 



CIRCDLATIOK OF FOKEIGX SUBSTAXCES IN THE BLOOD 

A series of interesting changes follows the injection of for- 
eign material into the blood stream. Various substances * 
either in solution or in suspension, when injected intravenously 
produce in a few minutes a profound leuoopcEnia, the majority 
of the polymorphonuclear cells disappearing from the periph- 
eral circulation and collecting in the blood vessels of the 
viscera, especially in the lungs and liver, and to a much smaller 
extent, in the spleen. Moreover, when material in suspension 
is injected, the foreign particles are also withdrawn promptly 
from the circulation and collected in the viscera, especially in 
the lungs, the liver, and to a less extent in the spleen. It is 
noteworthy that the leucocytes disappear simultaneously with 
the foreign material and collect in these same viscera. As a 
general rule, the leucocytes themselves are not destroyed, but 
after a comparatively short time — a few minutes to a few 
hours — they return, often in increased numbers, to the 
peripheral circulation. 

This distribution of foreign suspensions was thoroughly 
studied by Werigo ' ; he found that bacteria and also chemically 
inert particles such as carmine are promptly removed from the 
circulating blood. The essentials of these observations have 
been confirmed by Ewing.' Bruce ', in 1894, investigated the 
well known phenomenon of the more or less complete disap- 
pearance of the polymorphonuclear cells from the peripheral 
circulation after the intravenous injection of peptone; e. g., 
20 c. c. of a 10 per cent solution. It had been supposed that 
this sudden disappearance of the white cells was due to a cyto- 
lytic action of the peptone, but Bruce was able to show defi- 
nitely that the leucocytes collected in the blood vessels of the 
viscera, principally in the lungs, but also in the spleen, and in 
smaller numbers in the liver. The number appearing in the 
other organs, however, was almost nil, though the work of some 
authors indicates that the bone marrow is of some importance.t 
This similarity in the effect of peptone and foreign suspensions 
upon the distribution of the leucocytes suggests at once the 
possibility that the peptone may be withdrawn from the circu- 
lation corresponding in its behavior to that of suspended 
particles. Indeed it would be very helpful if the behavior of 
the leucocytes following the injections of a solution could be 
used as a criterion to determine whether the foreign substance 
in solution was distributed equally throughout the circulation, 
or whether it became concentrated in the viscera in a manner 
analogous to the behavior of foreign cells. 



* The earliest studies began in 1S72, observations being made 
upon tlie effect of such substances as curare, fibrin ferment, haemo- 
globin, septic fluids, lymph cells, split proteins, chemicals such as 
uric acid and the urates, and inert substances such as carmine. 
For detailed references see Sherrington, Proc. Ro.v. Soc, Lond., 
1S94, LV, 195. 

t Although there is some variation in the individual instances, 
yet the reports of the various authors indicate that the liver 
plays a distinctly more prominent part than the spleen in the 
retention of leucocytes and foreign substances, while the lungs 
play a more important part than the liver, presumably because 
material injected intravenously passes first throush the lungs. 



Experiments with Bacteria and Red Blood Cells. — The pos- 
sibilities of the full significance of these experiments and their 
bearing upon inoculation experiments in lower animals can be 
imderstood best by observing the course of events that follows 
the intravenous injection of bacteria. The following observa- 
tions were made in the course of the immunization of a rabbit 
against a staphylococcus of very low virulence. Upon the third 
injection, the 2-1-hour growth from 10 agar slants was emul- 
sified in 3 c. c. of salt solution and injected into a vein of the 
right ear. A blood smear was made immediately before injec- 
tion. The time required for injection was about two min- 
utes ; when it was completed, a blood smear was made from the 
left ear immediately and at successive intervals of 5, 10, 20, 
30, 40, and 60 minutes. The smear before injection showed 
an abundance of leucocytes in every field with 88 per cent of 
polymorphonuclear cells. The smears immediately after injec- 
tion showed very few white cells. In the smear five minutes 
after injection the majority of the fields under a 1/12 oil im- 
mersion lens were free from white cells. The differential count 
of 100 cells showed 96 per cent of mononuclear forms. The 
smear 10 minutes after injection showed increasing numbers 
of white cells over the preceding one ; this increase went on rap- 
idly and a smear 30 minutes after the injection did not dill'er 
in its general appearance from the one just before injection. 
No counts were made of the total number of white cells. 
The red cells were apparently unaffected. The behavior of tlie 
bacteria is even more interesting. With this massive quantity 
one would expect that they could be seen in the smears. How- 
ever, the smear made immediately after injection showed no 
bacteria, either free in the blood or in the few leucocytes that 
were present; but, in the smears in which the leucocytes were 
returning to the peripheral blood, staplwlococci were fre- 
quently found in the polymorphonuclear leucocytes ; some cells 
even contained too many bacteria to be counted readily. 

It happened that this animal had already received immuniz- 
ing doses of staphylococci ; on repetition with a normal animal 
essentially the same features were obtained, though not as 
sharjjly ; after considerable search only a few bacteria were seen 
in the leucocytes upon their return to the peripheral circula- 
tion. It was found, too, that such large doses often killed the 
animals suddenly during the course of the injection. Appar- 
ently no observations have been conducted to determine whether 
immunization or infection of an animal would definitely modify 
its l)ehavior in comparison with that of a normal individual. 
Any difference in a normal and immune animal in regard to the 
effect of foreign injections upon the distribution of the leuco- 
cytes would be very interesting, inasmuch as it would furnish 
a reaction for immunity which would be independent of any 
examination for immune bodies. Bull ' has recently studied 
very thoroughly the phenomena of agglutination in vitro and !« 
vivo. In many instances avirulent organisms are agglutinated 
in vivo in animals whose sera possess no agglutinating action in 
vitro. In contrast to these non-virulent organisms. Bull has 
made the further very interesting obsen"atiou that certain viru- 
lent organisms are not agglutinated in vivo by animals whose 
serum possesses no agglutinating power in vitro. In some 



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JOHNS HOPKINS HOSPITAL BULLETIN 



137 



respects it would be. difficult to distinguish agglutination in 
vivo from the phenomenon observed iu normal animals of the 
concentration of foreign particles in the viscera. 

Hopkins and Parker' have very recently noted that after 
intravenous injection streptococci are quickly withdrawn by the 
lungs, liver, spleen, and in small numbers by other tissues. 
These authors have contributed the following very significant 
observations. Some hours after injection streptococci, which 
cannot maintain themselves in the circulation of a normal ani- 
mal, begin to appear in the lilood stream. This occurs not- 
withstanding the fact that the inoculated animal has not lost 
its power of removing freshly injected organisms. 

On injecting typhoid bacilli, an organism ordinarily giving 
rise to leucopoeuia in man, we observed the same immediate 
results in rabbits as with staphylococci. Five agar slants of an 
old culture of B. typhosus were injected intravenously into a 
rabbit. The smears after injection showed an outspoken dim- 
inution in the number of white cells for a period of 20 minutes. 

Nucleated red cells upon injection behaved in the same gen- 
eral manner as other foreign agents, though the changes were 
less sharp. A half-grown rabbit was injected intravenously 
with 2 c. c. of a 50 per cent suspension of chicken corpuscles 
which had been washed twice with normal saline after collect- 
ing the blood in 1.5 per cent sodium citrate. The nucleated 
red cells could be seen in the blood smears in moderate num- 
bers for several minutes after the injection. No phagocytosis 
was seen at any time. The leucocytes of the rabbit also dimin- 
ished definitely. Counts were made at various intervals 
of the number of the red and white cells and the number 
of nucleated red cells with the following results : 

Table I. — Showixg the Red axd White Cou.n'ts and the Number 
OF Nucleated Reds After Intravenous Injection of a Rabbit 
WITH Chicken Corpuscles. 

Time in- Leucocyte Nucleated red count of 

tervals Red count count injected hen corpuscles 

4,500,000 5,500 

30 min.* 4,800,000 6,000 

3 min 600 42,000 

7 min 4,800,000 1,600 38.000 

18 min 5,100,000 2,900 12,000 

42 min 5,400,000 3,100 4,500 

IJ lirs 5,600,000 3,200 50 

2.i lirs 5,600,000 3,800 

3.J hrs 6,000,000 4,400 

5.J hrs 5,000,000 5.200 

* Injection : 2 c. c. of washed chicken corpuscles. 

The injection of mammalian (human) red cells, however, 
into a rabbit did not produce a leucopoenia. Certainly, there- 
fore, with the injection of red cells from the same species, as 
in the blood transfusions, one would not expect any immediate 
and pronounced leucopoenia. 

It has been shown by Goldscheider and Jacob ' that the sub- 
cutaneous injection of an emulsion of certain organs such as 
the spleen and also the thymus and bone marrow, produces an 
acute, transient, leucopoenia. We also found that the intraperi- 
toneal injection of pigeon corpuscles in a rabbit produced a 



definite, though less extreme, leucopoenia; however, this did 
not reach its most extreme grade till 20 minutes after the 
injection, and the white cell count did not return to normal till 
an hour had elapsed. 

THE INFECTIOUS DISEASES 

In considering the inoculation of diseases into animals, con- 
siderable interest centers in the natural distribution of par- 
asites in certain spontaneous infections. There is abundant 
evidence that when the blood stream is infected, the micro- 
organisms are not distributed equally throughout the blood. 
Thus, in typhoid fever, it is very probable that the concentra- 
tion of bacteria is greater in the spleen than in the peripheral 
blood and that they persist in the spleen after the circulating 
l)lood has become sterile. In connection with the comparative 
freedom of the extremities from rose spots in typhoid fever, 
it is interesting to note the apparent difficulty of reaching the 
peripheral parts of the body by injections into the blood 
stream. The malarial fevers furnish an excellent illustration 
of the irregular distribution of micro-organisms. In the 
sestivo-autumnal type, the parasites are concentrated in the 
spleen and bone marrow and it is only during the youngest 
stages of the parasite tliat the infected cells circulate freely 
in the peripheral blood. Perhaps one of the most striking 
and most perplexing examples of all is the profound variation 
in the case of infection with Filaria nocturna. This distribu- 
tion of pathogenic organisms should be borne in mind in 
attempting the transmission of infectious diseases to lower 
animals. 

Interpretation of Leucocyte Counts. — The consideration of 
the distribution of cells in the circulating blood is of signifi- 
cance in the interpretation of leucocyte counts. As early as 
1892 it was suggested by Eieder," and a little later by Schulz,' 
that tlie ordinary leucocytoses are due, not to an increased pro- 
duction of white cells, but to a redistribution of them, the cells 
from the blood spaces being called out into the peripheral cir- 
culation at the time of an infectious process. Although this 
view certainly does not apply to all cases, there are many 
instances in which it is seen that sudden changes occur in the 
leucocyte count which are due, not to the formation or destruc- 
tion of cells, but to a redistribution of the cells in the body. 
Lowit," in 1892, expressed the prediction that a leucopoenia 
probably preceded the leucocytosis in many infections, in a 
manner somewhat analogous to these experimental leucopce- 
uias and leucocytoses. This view received prompt confirma- 
tion by Sherrington," and others. There are numerous exam- 
ples of the development of a leucocytosis, under clinical con- 
ditions, in a space of time much too short for tlie production of 
new cells. In intestinal obstruction there is often a sudden 
outpouring of adult polymorphonuclear cells, producing a rise 
in the white count to 30,000 cells, or more, within five or six 
hours. Furthennore, there is the example, previously men- 
tioned, of the doubling of the leucocyte count iu a few hours 
after a cold bath. Although the e.xact time required for the 
multiplication of some of the lowest types of bacterial cells 
is extremely short, yet it is obvious that tlie sudden changes in 



138 



JOHNS HOPKINS HOSPITAL BULLETIN 



[Xo. 328 



the number of blood cells are not due to a destruction and 
formation of corpuscles, but to a redistribution of cells already 
existing in the body. At the beginning of an acute leucocytosis 
the polymorphonuclear cells -which appear are mature in their 
morphology and do not have the appearance of being young 
and freshly formed. Similarly, in the experimental leuco- 
poenias there is no reason to assume a sudden destruction of 
leucocytes; the injected material in most instances is not toxic 
in vitro for leucocytes and there is no evidence in the morphol- 
ogy of the leucocytes of any toxic action in vivo. 

The preceding data afford ample ground for the conclusion 
that the leucocyte counts must be considered as indicating 
only the number of cells at a given time in the peripheral circu- 
lation and not as an index of the absolute number in the entire 
body. Thus, it is not Justifiable to conclude, a priori, that there 
is a destruction of leucocytes in typhoid fever. The leucopceuia 
which develops might readily lead to the assumption that there 
is an extensive destruction of white cells. The observations of 
Thayer," however, show that a mild physiological stimulus 
will promptly raise the number of leucocytes at least to the 
upper limits of normal. As far as the leucocyte count of the 
peripheral blood in typhoid fever is concerned, it is obvious, on 
theoretical grounds, that the absolute number of leucocytes in 
the body may be either diminished, normal, or increased. 
The determination of the exact condition must be made by 
means other than the- examination of the circulating blood. 
The evidence bearing on the question is very meager, but, as 
far as it goes, it would seem at least possible that the absolute 
diminution of leucocytes in typhoid may be much less than 
one has ordinarily supposed. 

Moreover, the infecting organism is not the sole factor 
which influences the white cell count. It is well known that 
the severity of the infection is important. Thus, pyogenic 
organisms, which ordinarily produce a leucocytosis, may, in 
hyperacute infections, produce a leucopoenia ; if one accepts tlie 
work of Sherrington this would mean that the initial leu- 
copoenia which often occurs very early in the course of a 
pyogenic infection may persist in the severe cases instead of 
giving place to a leucocytosis. There is also another factor 
which requires consideration ; Emerson " has noted that the 
same organism may produce different effects, according to the 
location of the lesion in the body. Thus, in the after effects of 
typhoid fever, a peripheral lesion such as may occur in the 
bones is accompanied by a leucocytosis. This also affords 
an instance in which typhoid infection is not accompanied by 
any manifest destruction of leucocytes. Tuberculous infec- 
tions also indicate that the location of the lesion in the body 
rather than the infecting micro-organism may sometimes be 
a determining factor in the effect on the leucocyte count. 
Thus milary tuberculosis may be accompanied by a leucopoenia, 
whereas tuberculosis of the meninges usually produces a 
leucocytosis. The examples afforded by tuberculosis, however, 
are often complicated by the possibility of secondary infection. 
Apparently there is no crucial experimental demonstration 
of these clinical observations that the location of the lesion may 
occasionally be the determining factor in the leucocyte count. 



PART II. SPECIAL CONSIDERATIONS REGARDING THE 
TRANSMISSION OF INFECTIOUS DISEASES 

It woiild seem that the diseases to which lower animals are 
naturally susceptible by intravenous, subcutaneous, or intra- 
peritoneal inoculation have already been determined, at least 
for the more important infections. A further extension of the 
ability to transmit diseases to relatively insusceptible species 
would, in most cases, involve either a modification of these 
simpler methods of inoculation, or special preparation of the 
new host. There are many arguments which may be advanced 
against intravenous injection. In the first place, there is 
necessarily considerable dilution of the infective material with 
an extremely good opportunity for the operation of any deleter- 
ious action which the plasma and cells of the blood may pos- 
sess. A priori, intravenous injection would seem to be ideal 
in its possibility of reaching all the organs of the body. How- 
ever, the foreign material is not only collected primarily in 
the lungs, liver, and spleen, but the phagocytic cells of the 
blood also collect ip. these areas. Moreover, the mechanical 
disadvantages are not inconsiderable, since the material intro- 
duced must be reduced to a fine suspension on account of 
the danger of embolism; even with a fine emulsion, massive 
injections for the purpose of overwhelming an animal are often 
inadvisable on account of the danger of immediate death. 

In recent years, not a little attention has been given to the 
concentration of infective agents in locations of special sus- 
ceptibility just as therapeutic agents are introduced at the 
principal site of local infections, as in the routine intraspiuous 
treatment of cerebrospinal meningitis, and in the treatment 
of tabes by Swift and Ellis." It seems logical to introduce the 
infective agent into the locations which are involved in spon- 
taneous infections, as in the case of the experimental produc- 
tion of anterior poliomyelitis by inoculation into the central 
nervous system, or the reproduction of tuberculosis and 
syphilis by inoculation into the testes. 

CHOICE OF THE SPLEEX FOR IXOCULATION EXPEPvIMENTS 

An attempt has been made to take advantage of some of these 
special methods of inoculation in some experiments on the 
transmission of leukaemia to lower animals. For the inocula- 
tion of lower animals, the spleen was selected as the site of 
injection, not only because this organ is involved in leukaemia, 
but because it frequently harbors various parasites. At the 
same time it cannot be regarded as a site of especially low 
resistance in view of the opportunity for the action of the 
fluids and cells of the blood in its sinuses and also on account 
of the phagocytic cells characteristic of the spleen itself. 
Nevertheless, it is a convenient location for concentrating a 
large amount of infective tissue in preference to the injection 
of a comparatively few isolated cells into the blood stream. 
The spleen is easily exposed by a laparotomy done, of course, 
under ether. In some animals, especially in cats, it was found 
that large blebs of the injected material, measuring 1 or 2 cm. 
in diameter, can be produced under the capsule of the spleen. 
Since these blebs are not rapidly absorbed, their contents 
would naturally be much better protected from the immediate 



June, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



139 



action of the blood serum and the leucocytes than they would 
in the case of intravenous injection. There is also considerable 
mechanical advantage in making injections directly into the 
spleen ; large pieces of tissue, such as would be altogether un- 
suitable for intravenous work, can be introduced into this 
organ. The spleen readily filters out tlie grosser particles ; in 
a large number of instances we have had no evidences of embo- 
lism in the injection into the spleen of coarse suspensions 
of various tissues. 

From a clinical standpoint the spleen of some animals, 
notably the monkey, is an excellent organ for observation, since 
its size can be easily determined by palpation, thereby enabling 
one to detect very readily a splenomegaly. The advantage 
of this is evident, both in those cases in which a change in 
the blood picture occurs, and also during any intervals in 
which the blood picture is normal while the spleen is enlarged. 

Direct inoculation into the spleen and other organs has 
been practised in a variety of conditions. Musgrave and 
Clegg " attempted to produce amoebic hepatitis by direct injec- 
tion into the liver of cultures of the limax group growing 
with B. typhosus. Mackie" inoculated Leishmania tropica 
into the liver and spleen and v. Seht" reported the inocula- 
tion of leuktemic blood into the spleen of monkeys. All of 
these injections into the viscera resulted negatively. Patton '* 
obtained some positive results by the direct inoculation of 
Leishmania donovani into the liver. 

IXOCULATIOX EXPERIMENTS IX LEUKAEMIA 

Our own work has been confined to the inoculation of mate- 
rial from various types of splenomegalies into several species 
of animals. For the most part we confined our attention to 
acute and subacute leukeemias. There is considerable choice 
in the selection of material for inoculation. In the patients 
who were studied, we have used blood for inoculation as a 
routine, and in one instance some enlarged glands. No patients 
were available in whom the spleen was enlarged in a suitable 
manner for puncture and aspiration. In one autopsy case, 
splenic tissue was obtained for injection. In all, five cases 
of leukaemia were studied; from four of these blood was 
injected into the spleen of cats, monkeys, and rats. There was 
frequently considerable disturbance of the blood picture dur- 
ing the first two or three weeks after the injection. The most 
prominent characteristics were a rise in the leucocyte count, 
the appearance of unusual cells in the circulation, and fre- 
quently an increase in the number of platelets with the appear- 
ance of many large forms. Injection of normal blood did not 
produce such changes. The eft'ect of leukemic blood was not 
constant, however, and in no case did it produce a picture of 
leuka?mia. In one instance enlarged glands from a case of 
acute leukfemia were injected but no definite effect was pro- 
duced. At most the results were never more than suggestive, 
and consequently a full report of these cases will not be made 
at present. One case which came to autopsy, however, deserves 
special consideration. 



ACUTE LEUK.EMIA 

This case was seen through the kindness of Doctors Leopold 
and Sexton at the Hebrew Hospital. The patient was a man 
in the thirties, of rather robust constitution. The total course 
of his disease was of only a few weeks' duration and he came 
to the hospital in the last few days of his illness. On admis- 
sion he was semicomatose and presented at this time the 
typical clinical features of an advanced pernicious anaemia. 
There was a moderate degree of jaundice. The spleen and 
liver were not palpable. The blood picture, however, was by 
no means a simple one. 

The red colls were diminished to 1,500,000 per c. mm. and 
there was a proportional reduction of haemoglobin. Only a 
moderate grade of anisocytosis and poikilocytosis was present. 
Normoblasts and megaloblasts were abundant. The white 
count was high, varying from 22,000 to 24,000. Of these 
cells about 2000 were nucleated reds and of the remainder, 
60 per cent were jDolymorphonuclear in type. There were 
many rather unusual mononuclear cells but only an occasional 
myelocyte was seen. 

There was nothing remarkal)le about the platelets either 
in their morphology or numbers. 

The case was clearly an unusual one but seemed to conform 
most nearly to that group of acute leuksemias which tend to 
go over into a fairly typical pernicious anaemia. 

Direct transfusion of blood produced only a very transient 
benefit, and exitus occurred a few days after admission to 
the hospital. Five hours after death the spleen was removed ; 
it was only slightly enlarged. Aerobic and anaerobic cultures 
of small pieces of splenic tissue on ascitic fluid, blood serum, 
Dorsett's egg medium, blood agar (NNN medimn), and milk, 
remained sterile for a period of three weeks. A coarse emul- 
sion of the spleen in salt solution was injected into some ani- 
mals. The following is a general summary of the results 
which were obtained. 

A cat inoculated into the spleen died on the si.xth day after 
injection. The spleen of this animal was inoculated intra- 
splenically into a young adult cat which died on the sixth day 
after injection. Subinoculations were made intrasplenically 
into a monkey from the spleen of this eat. Three weeks later 
the spleen of the monkey had increased to several times its 
normal size and the blood picture was characteristic of lym- 
phatic leukaemia. The temperature of the animal was high 
being 104° and 105°F., but this is not very unusual in normal 
monkeys. Splenic tissue removed at this time failed to pro- 
duce any change in a second monkey. The blood picture 
returned rather rapidly to normal, but the spleen remained 
large for many weeks. This animal died 15 months later. The 
autopsy revealed no apparent cause of death. The protocols 
of these experiments are as follows. 

A monkey and a cat were injected intrasplenically with the 
patient's spleen. This material was highly toxic for the mon- 
key, death taking place within two or three minutes after the 
injection from cardiac failure. The cat recovered from the 
operation but became somewhat ill in a few days, coma develop- 



140 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 328 



ing on the sixth day after injection. Blood smears taken 
when the animal was in complete coma showed a remarkable 
picture in that the leucocytes were practically absent. The 
ordinary preparation for leucocyte counting showed no cells 
in a 0.1 sq. mm. unit. Blood cultures on milk showed a growth 
of a micrococcus in one of three tubes, indicating a secondary 
bacterial invasion. This animal was sacrificed just before 
death and subinoculations were made, spleen, blood, and bone- 
marrow being used, one cat being employed for each sub- 
stance. All of the animals remained perfectly well except the 
one receiving an injection of spleen. This animal died on the 
sixth day and blood smears made a few hours before death also 
showed a complete absence of leucocytes. This is open to the 
interpretation that in the acutely fatal cases some leucotoxin 
produced extensive destruction of the white cells. A simpler 
explanation, however, suggests itself, since in some instances 
control animals injected with large doses of bacteria also 
showed when in the stage of coma a similar absence of leuco- 
cytes. Cultures from the heart blood of this second cat showed 
prompt growth on milk. The spleen itself showed no gross 
changes ; small portions were emulsified and injected into the 
spleen of a monkey {Macaciis rhesus). This cat died after 
three days from a complicating peritonitis whereas the monkey 
remained apparently well. The operative incision healed 
promptly with no evidence of any secondary infection. The 
white blood counts showed some fluctuation, but no signifi- 
cance could bo attached to them. The count fell at first from a 
normal of 27,000 to 13,000. During the next three weeks it 
rose gradually to 56,000, a significant change occurring in the 
differential. In this species of monkey, the mononuclear ele- 
ments are normally very high as compared with man ; a typi- 
cal count of this individual before injection showed 35 per 
cent polymorphonuclear cells, and a total of 57 per cent mono- 
nuclears with 8 per cent of cells unclassified. During the rise 
in the white count, however, the polymorphonuclears fell to 
19 per cent, and the mononuclears rose to 81 per cent. Taking 
fully into consideration the normal blood picture of the Maca- 
cus rhesus, the smear was distinctly characteristic of a leu- 
kaemia of the lymphatic type. The evidence of a leukremie 
change as contrasted with a leucocytosis was seen, both in tlie 
low percentage of polymorphonuclear cells in the blood and 
in the appearance of some immature cells, such as a few myelo- 
blasts. These cells were not found in the normal blood of this 
individual before injection and in the examination of 10 
other macacus monkeys they occurred only in a few individ- 
uals and in very small numbers. This change in the blood 
picture lasted for several days and then returned to nonnal. 
In addition to the change in the blood picture a well marked 
splenomegaly developed. Three weeks after the injection, the 
spleen was found to be several times larger than its normal 
size. On exploration, this increase in size was found to be 
due, not to swelling and congestion, for the .spleen was hard 
and firm, measuring four times its size before injection. On 
surgical extirpation of about one-fourth of the organ, it was 
so firm that relatively little lifemorrhage took place. Histo- 
logically tlicrc was nothing remarkable. 



This splenic tissue obtained by operation was injected into 
the spleen of a monkey and into a kitten. Cultures were 
also made on blood agar, on ascitic fluid containing fresh 
tissue and on Dorsett's egg medium. The animals remained 
well. During the next three months no significant change 
occurred either in the blood count or in the size of the spleen. 
The cultures were observed for three weeks but no growth 
developed. 

Some control obser\-ations were made in order to determine 
as accurately as possible the cause for the enlargement of the 
spleen and the change in the blood occurring in the monkey. 
It is important to eliminate the ordinary bacterial cau.ses 
especially secondary pyogenic infection and tuberculosis. 

Apparently a few bacteria were present in the cat's spleen 
which was injected into the monkey, since the blood of this 
cat showed growth in milk of a coccus. This is an unfor- 
tunate circumstance but secondary infection in a moribund 
animal readily develops. These organisms apparently were 
not present in the patient's spleen since the cultures on various 
media showed no growth. There is considerable evidence that 
this organism could not have been responsible for the change 
observed in the monkey. An absolute increase in mononu- 
clear cells is not a characteristic of pyogenic infection ; and 
moreover there was no evidence of any local or general sepsis. 
Finally a control experiment was done injecting 2 c. c. of a 
milk culture of this micrococcus into the spleen of a normal 
monkey. A typical pA'Ogenic leucocytosis resulted. The leu- 
cocytes rose in 24 hours from 8000 to 10,000 and the propor- 
tion of polymorphonuclear cells rose from 36 to 95 per cent. 
The blood picture gradually returned to normal and the spleen 
did not enlarge. Ten months later this animal developed 
several metastatic abscesses. The spleen did not enlarge and 
the white count rose to 59,000 with 90 per cent polymorpho- 
nuclear cells. He soon recovered from these infections. 

If there were any evidence by which the production of the 
leukannia picture could be ascribed to the bacteria present, it 
would be an extremely interesting factor in bringing about 
the correlation of the leucocytoses with the leukjemias, since 
the hypothesis has been advanced that the two conditions are 
jDart of the same process, and that the same agent, if allowed 
to act for a long period, may produce first a leucocytosis, and 
subsequently, with the exhaustion of the bone marrow, a leu- 
kffimic picture may develop. 

The consideration of tuberculosis is important and fortu- 
nately it can be excluded rather readily. In the first place 
this monkey developing a splenomegaly, lived for many months 
after this experiment and when death eventually occurred, 
the autopsy showed no evidence of either active or healed 
lesions of tuberculosis. Moreover, when the spleen had reached 
its maximum size, a portion that was excised sliowed no 
histological evidence of tuberculosis and no growth developed 
on appropriate media. A second monkey inoculated with the 
tissue did not develop tuberculosis. 

From the data which have been presented the conclusion 
naturallv follows that tlie ciilar,i:cnient of the spleen accom- 






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141 



panied by the leukfemic blood picture could not be attributed 
to pyogenic infection or to tuberculosis. 

This leukannic change was of short duration and could not 
be transmitted by subinoculation. Nevertheless it is of inter- 
est in view of the many entirely futile attempts to produce 
either leukaemia or splenomegaly experimentally. 

It is perhaps a little difficult to form a distinct impres- 
sion of the difference in these blood pictures simply from an 
analysis of the total and the differential counts. Accordingly 
we have reproduced typical fields from three of the more im- 
portant preparations: namely, of (1) a normal monkey; (2) 
the same monkey after injection with material coming origin- 
ally from a case of leukiemia in man; and (3) the reaction of 
a monkey to pyogenic bacteria. 

SUMMARY 

I. The circulation of normal and foreign substances in the 
blood often fails to follow mechanical laws, either under nor- 
mal or pathologic conditions. An unequal distribution occurs 
which is governed by biological conditions. The corpuscles 
of the blood are not distributed with mechanical unifonnity 
throughout the blood channels; parasites invading the blood 
stream are often concentrated in the blood spaces of the viscera. 

II. Upon injection of a variety of substances into the cir- 
culation, the injected substance and the leucocytes, especially 
the polymorphonuclears, disappear from the peripheral cir- 
culation within a few minutes and collect in the blood vessels 
of the viscera principally in the lungs and liver. Within a 
short time the leucocytes return to the peripheral circulation, 
often in increased numbers and sometimes after having phago- 
cyted the injected material. 

III. The leucocyte count cannot be interpreted as an index 
of absolute change in number of leucocytes in the entire body, 
for it often indicates only changes in distribution rather than 
a formation or destruction of white cells. Thus, the total white 
count does not constitute crucial evidence that there is an abso- 
lute leucopocnia in typhoid fever. There are at least three fac- 
tors governing the leucocyte count; namely, (1) the infecting 
organism; (2) the severity of the infection; and (3) the loca- 
tion of the infection in the host. 

IV. The failure of foreign substances to be distributed in 
the blood stream according to mechanical laws has an impor- 
tant bearing on the transmission of infectious diseases. It 
offers many arguments against intravenous injections of infec- 
tive material for the transmission of a disease to resistant 
animals for the reason that, 

1. Considerable dilution of the material necessarily 
occurs. 

2. Extensive opportunity is offered for the action of 
any deleterious effects which the fluids and cells of the 
blood may exert. 

3. Fine suspensions and limited amounts of material 
are necessary in order to avoid embolism and sudden 
death. 



4. Finely suspended matter is not distributed equally 
throughout the blood stream, but a large proportion is 
removed by the lungs. 

Many of these objections could, of course, be overcome 
by an intra-arterial injection if it were made into the 
proper side of the circulation. 

V. Inoculation into the spleen for the transmission of sple- 
nomegalies to lower animals possesses certain advantages : 

1. It avoids many of the disadvantages of intravenous 
injection. 

2. The injected material can be temporarily protected 
from the immediate action of the fluids and cells of the 
body. 

3. The mechanical advantage is considerable, since 
large pieces of material can be used. 

4. The spleen is well adapted for study, since changes 
in its size in certain animals can be readily determined 
by palpation. 

VI. Inoculation of the spleen of a case of acute leukeeraia 
into the spleens of cats produced death acutely. Inoculation 
from these cats into a spleen of a monkey produced a chronic 
splenomegaly with an acute temporary leukemic change in the 
blood jjicture. The production of even abortive leuksemic 
changes and of splenomegaly in a normal animal by inocula- 
tion of human material is of interest. 

This work was conducted during 1914 in the clinic of 
Prof. Lewellys F. Barker at the Johns Hopkins Hospital. A 
report was made at that time before the Johns Hopkins Medi- 
cal Society. In the meantime the continuance of these studies 
has been seriously interrupted and has finally been suspended 
for the time being. Consequently, it has seemed advisable to 
make this incomplete report without waiting for confirmation 
and extension of these results. It is a pleasure to thank Dr. 
Barker for a helpful and stimulating interest. 

DESCRIPTION OF ILLUSTRATIONS 

RO.MANOWSKT StAIX (WiLSO.n's) 

Fig. 1. Typical field from blood smear of normal monkey. 

Fig. 2. The same monkey three weeks after inoculation with 

splenic tissue from an animal injected with the spleen 

from a case of leukaemia in man. 
Fig. 3. Control monkey inoculated with pyogenic organisms to 

show the effect on the blood picture. 

LITERATURE 

1. Lamson: Jour. Pharmacol, and Exper. Therap., 1915, VII, 
169; 1916, VIII, 167. 

2. Werigo: Ann. de I'Inst. Pasteur, 1S92, XVI, 478. 

3. Ewing: New York Med. Jour., 1895, LXI, 257. 

4. Bruce: Proc. Roy. Soc, Lond., 1894, LV, 295. 

5. Bull: Jour. Exper. Med., 1915, XXII, 475 and 484; ibid., 1916, 

XXIV, 25. 

6. Hopkins and Parker: Jour. Exper. Med., 1916, XXVII, 1. 

7. Goldscheider and Jacob: Ztschr. f. kiln. Med., Berlin, 1894, 

XXV, 373. 

8. Rieder: Beitr. z. Kennt. d. Leucocytose, Leipzig, 1S92. 



142 



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[No. 328 



9. Schulz: Deutsch. Arch. f. klin. Med., 1893, LI, 234. 

10. Lowit: Studien z. Physiologie u. Pathologie des Blutes u. d. 
Lymph., 1892. 

11. Sherrington: Proc. Roy. Soc, London, 1894, LV, 161. 

12. Thayer: Bull. Johns Hopkins Hosp., 1893, IV, 37. 

13. Emerson: Clinical Diagnosis, First Edition, 1906, 565. 



14. Swift and Ellis: New York Med. Jour., 1912, XCVI, 53. 

15. Musgrave and Clegg: Philippine Jour. Sc, 1906, I, 909. 

16. Maekie: Brit. Med. Jour., 1907, 1363. 

17. V. Seht: Z. Pathogenese d. Myeloiden Leukamie, Inaug. 
Dissert., Marburg, 1913. 

18. Patton: Indian Jour. Med. Research, 1913, I, 185. 



MEMORIAL MEETING TO DR. THEODORE CALDWELL JANEWAY 



A memorial meeting for Dr. Theodore C. Jaiieway, late 
Profes.sor of Medicine to The Johns Hopkins University and 
Physician-in-Chief to the Hospital, was held in the hall of the 
Engineering Building of the university at Homewood, on Sun- 
day afternoon, March 10. The meeting was opened with 
prayer by Eev. Dr. Arthur B. Kinsolving, and addresses were 
made by President Frank J. Goodnow, Johns Hopkins "Uni- 
versity; Mr. B. Preston Clark, Boston, Mass.; Dr. John 
Howland, Johns Hopkins University; Dr. Alexander Lam- 
bert, Dean of the Medical School of Columbia University; 
Dr. David Edsall, Harvard University ; Major General William 
C. Gorgas, Surgeon General, U. S. Army, and Dr. AVilliam H. 
Welch, Johns Hopkins University. 

Rev. Dr. Arthur B. Kinsolving. — God our Father, from 
wliom we conu'. to whom we go, in who.se gracious protection 
Thy children abide in whatsoever place and condition they 
may be; we thank Thee for all the goodly company of those 
who have helped us by their eminent labors and noble examples. 

We yield unto Thee high praise and hearty thanks for the 
graces and virtues of him we are met to memorialize, for the 
beneficent skill of the good physician, for the diligent man of 
science and research, for the fearless follower of truth, for the 
strong and inspiring friend, for the devout Christian who amid 
his thronging duties made room in his life for God, for the citi- 
zen who withheld not his life at his country's call. 

Help us each to -grow stronger, more gentle, brave and true 
by calling to remembrance his gifts of thought and speech, hi.s 
quick and understanding sympathy, his vision of service, and 
duty. Grant that all that he was here may be ripened and 
expanded there, and that he may find employment in the spa- 
cious fields of eternity. 

Help us all, God, to rejoice more and more in other 
men's strength and brightness and success, and set our hearts 
free to serve Thee better, and more perfectly to love Thee, 

Through Jesus Christ our Saviour. 

President Frank J. Goodnow. — We have come together this 
afternoon to honor the memory of Theodore Caldwell Janeway 
whose death in the service of his country has caused such a 
vacancy in our ranks. 

Prior to the breaking out of the war, to the prosecution of 
which Dr. Janeway gave so much of his time and strength, he 
had won an enviable reputation as practitioner, teacher, or- 
ganizer and student. His love for the scientific side of his 
profession was so great that when the opportunity presented 
itself he gave up active practice to devote his entire time to 
teachimj and investigation. At the time (his countrv entered 



as a participant in the great conflict now raging, he had suc- 
ceeded in putting his department in the Hospital and Medical 
School in a state of rare efficiency. 

The call of his country could not, however, be denied. The 
extra duties which he then assumed were a great addition to 
already' burdensome responsibilities. His regretted death cut 
him off at the height of his usefulness. It leaves us, his friends, 
however, with the consolation that the standards he set will 
live long after he has gone out of our lives. We mourn the loss 
of a kindly presence. We cherish the memory of a sincere per- 
sonality, a strong character, an able man. 

Mr. B. Preston Clark. — It is entirely natural that we who 
know and love Theodore Janeway should each know best some 
special side of that nature, which touched life .so profoundly, 
and from so many angles. 

Though he and I have known each other for less than ten 
years, it seems as though we had always known each other. 

My first meeting with him was after a remarkable diagnosis. 
The patient, one of my own boys, was recovering from a serious 
illness. I tried to express my gratitude as best I could, and in 
that quick way of his he said "Most of the agencies that make 
for human health and disease are microscopic in their charac- 
ter, and we really know very little about any of them." That 
attitude of simple humility toward the profession of which he 
was a master I can never forget. 

I have not the knowledge, as so many here to day have, to 
gauge in any broad way his professional skill, I being only a 
layman, a business man. I only know that it must have been 
wonderful. It has been on other .sides that I have known him. 

When some difficult and intricate industrial problem has 
been under consideration, I have taken the opportunity when 
it was possible to discuss it with him. And we never had such 
a discussion without my learning much from his method of 
approach which helped to clarify the issue and to assist in 
finding a solution. For his mind had a universal quality. 

Of just one other quality of his vivid personality I shall 
speak and only one. And that is his apprehension of the invis- 
ible and the spiritual as being more truly real than aught 
which we can touch or handle. That is to me the crown of 
his personality and its very essence. 

During this last summer on his short vacation we lost no 
moment when we could be together, and the same was true on 
my own hurried trips to Washington during the early winter. 
And always I was conscious in him of a great and increasing 
power of leadership. 

Leadership is a subtle and elusive thing, not to be limited 
or exactlv defined. But of one thinir we can be sure. The 



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PLATE XIX 




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JOHNS HOPKINS HOSPITAL BULLETIN 



143 



great loader cares so deeply for his cause; he sees his vision 
so clearly, that he forgets himself. He sacrifices himself with- 
out knowing that he is doing so; he sees in sacrifice simply 
boundless opportunity. He draws men after him ; because they 
follow, not him alone. They follow that which he follows. As 
in the battles of old the fighters followed the gigantic shadowy 
"warrior who led them to victory. 

And when in battle a leader, a true leader, falls, the charge 
cheeks for perhaps a brief moment, but it goes forward with 
undiminished power, and the charge is driven home. 

Such a vision of the invisible and the eternal was given to 
Theodore Janeway ; such a leader he was and is ; and may it be 
given to us in the light of that vision to follow that which he 
followed ; to raise aloft the standard which has fallen from his 
band; to see in sacrifice simply opportunity; to live worthily 
of the vision, to close up the ranks, and to carry the charge 
home. Thus shall we pay a living tribute to a great leader, 
and a yet greater man. 

Dr. John Howland. — For many years I have known and 
admired Theodore Janeway. We were boys together at school, 
■vve were at college and in the medical school at the same time, 
we were contemporaries in New York and, finally, were col- 
leagues in Baltimore together. I may speak of him, then, 
in many stages of his career, for I saw him grow from a school- 
boy into a man and finally become a leader of medicine. 

On looking back, it is easy to see that he exhibited strikingly 
as a boy the qualities that made him distinguished as a man. 
There was nothing that he had to put behind him or forget or 
outgrow, nor was there an abrupt change from the irresponsi- 
bilities of youth to the duties of later life. It was just a grad- 
ual, even growth and development in a life of singular recti- 
tude. 

Pie was, in school and college, conscientious, persevering and 
serious. He matured early. He was studious and always a hard 
worker but there was nothing of the book-worm about him. 
He was merry and keen in regard to all the activities of scliool 
and college life. Cheerful and well liked by all, he gave the 
gift of his intimacy to but few. 

Thus, Janeway went through college, leaving behind an 
enviable reputation in those courses that jDrepare for a medi- 
cal career, for he early knew what his profession was to be, and, 
alive to the responsibility of one who bears a distinguished 
name and also because he believed in doing all important 
things well, he worked with characteristic diligence and enthu- 
.siasm. Those who taught him could outline his future. 

It was, however, in his medical school course that he really 
shone. He was the first or second man in a singularly good 
class and, by virtue of this fact, became eligible to compete for 
a number of prizes of very considerable money value. Then he 
did a characteristic thing, the reason for which was only 
surmised and of which he never spoke to any one. He did 
not compete for the prizes. It was quite plain that he would 
have been successful and he must have known it for he judged 
fairly his own abilities though he never overestimated them. 
But he knew there were others wlio needed the reward more 



than he. Such consideration for others was not an isolated 
example. It was a constant and conspicuous trait of a gener- 
ous spirit, exhibited throughout his whole life. 

He served through his hospital years with great credit and 
then began the practice of medicine with his father. It is 
seldom that any one is fortunate enough to work under such 
inspiration and guidance. Dr. Janeway, the elder, was a 
medical man in a generation. He had intuition, great knowl- 
edge, his experience was enormous and his judgment unerring. 
Between him and his son there was complete community of 
spirit and entire intellectual sympathy. 

It is one of the regrettable things in medicine that a master 
of diagnosis cannot transmit his experience to succeeding gen- 
erations. His knowledge he may, in books and pamphlets; 
his experience usually dies with him unless the opportunity 
is given to the pupil, by close and constant association, to see 
repeatedly the attitude of mind toward medical problems and 
thus to absorb some of the mental processes of the master. 
This opportunity was given to Theodore Janeway and was 
eagerly utilized. The years that they were together must have 
been a period of intense enjoyment and a wonderful experi- 
ence for both father and son. They were absorbed day after 
day in entire accord upon the work that interested them most. 

It was a period of rapid growth for Theodore Janeway, so 
rapid that it became in a short time evident to all his contem- 
poraries that he was to be a man of prominence and this con- 
viction steadily grew; for it was readily recognized that he 
was not only a diagnostician of great skill, always sound and 
often brilliant, but that he was a capable experimenter and an 
especially gifted teacher. 

He began to teach first in a minor capacity at The Uni- 
versity and Bellevue Medical College and later he advanced to 
more important positions until he finally was called to the 
Bard Professorship of iledicine at the College of Physicians 
and Surgeons. 

To all forms of teaching he added something new, some- 
thing that made the subject more interesting, more stimulat- 
ing. In the teaching of physical diagnosis, he introduced sim- 
ple mechanical experiments to demonstrate the principles of 
physics underlying the signs. He was the first in New York 
City to teach medicine from the standpoint that disease is a 
deviation from the normal physiological basis and he, together 
with Oertel, introduced, at the City Hospital, the clinical- 
pathological conference, a form of exercise that has been 
widely adopted. And it should not be forgotten that in this 
country the clinical study of the blood pressure began with 
him and that he devised the first instrument that made the 
study of this possible for us at the bedside. 

Janeway, at one time or another, was connected with a num- 
ber of different dispensaries and hospitals. Many of the ser- 
vices he reorganized and all were improved by better methods, 
greater service and more complete cooperatiDU. '\\hen he 
went to the City Hospital on Blackwell's Island, the service 
was neglected, the internes were poor in ability and bard to 
obtain. In a short time, everj-thing was changed so that it 



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was an active, most effective organization with men eagerly 
striving for positions upon his staff. 

Occupied as he was with teaching, research, hospital work 
and practice, he, nevertheless, found time to give advice and 
assistance to the charitable organizations that try to improve 
the conditions of those incapacitated for work by accident 
and disease. He appreciated the distress that frequently ac- 
companies disease and he felt that he could and would con- 
tribute to an intelligent amelioration of this. For many 
years he was closely identified with the Association for Improv- 
ing the Condition of the Poor. 

In all his work, indeed in all his life, he was as conscientious 
as a man could be. He was thoughtful of others, he made 
the way easier for many but he would not spare himself. He 
worked incessantly and constantly beyond his physical capacity. 
He could not be persuaded to do less. It was part of his 
creed that if things were to be done, they were to be done 
well no matter at what cost to himself. He was mentally 
sound and he was ruggedly honest with all and especially with 
himself. He practiced medicine and he taught medicine hon- 
estly. If there were an error in diagnosis, he was always the 
first to acknowledge it ; he would claim no part in any work 
that was not his own, and he could teach medicine only upon 
the basis of established fact. To those who knew him, he was 
a loyal and devoted friend, a companion full of humor but 
also of inspiration. And so I felt and shall always feel that 
when Theodore Janeway died, at the height of his ability and 
usefulness, medicine suffered a grievous loss and a splendid 
man was gathered to his fathers. 

Dr. Alexander Lambert. — In New York we of the medical 
profession have never ceased to look upon Theodore C. Jane- 
way as one of us and to regard him as a New Yorker. Out- 
side of the profession the city still asks for him for advice 
although he has been away from his inherited professional 
haunts for nearly four years. New York has never been with- 
out a Doctor Janeway for more than fifty years and that city, 
in spite of its two hundred new citizens each day, is a city of 
habit and tradition especially in medical affairs. A consulta- 
tion with Doctor Janeway was a habit so ingrained that it is 
not yet quite broken, at least in the thought and subconscious 
longing of the population. This habit was founded by Theo- 
dore Janeway's father who won the position of first con- 
sultant in New York by giving a careful study to each problem 
presented to him before drawing upon his remarkable experi- 
ence in the pathological amphitheater and the clinical wards 
of the three great hospitals which he had served. 

New York medicine, to a superficial view, often seems 
tainted with commercial methods, harassed by professional 
competition and hampered in development because its suc- 
cessful practitioners of the medical art are broad catholic citi- 
zens of the world and not intensive scientific investigators. 
Such a judgment is truly superficial for the influence of New 
York has been widely spread through the United States by 
the activity in the teaching hospitals of the city of certain 
great personalities who stood for an ideal to make the practice 



of medicine a humane art applied to lumian beings by human 
beings. 

Both Janeways, father and son, represented this class in the 
metropolitan community — Edward G. Janeway exerted his 
greatest influence in this broad New York way upon many 
generations of students from all the colleges of the city and 
from many outside of it as a physician of Bellevue Hospital 
and not in any narrow field limited by academic walls. 

Theodore C. Janeway inherited a remarkable memory which 
he trained to store up both the facts to be found in medical 
literature and also the varied clinical pictures that were con- 
stantly being brought to his father's office for interpretation. 
In that office under that chief he developed a great diagnostic 
insight which however he never allowed to lead him across lots 
to his goal without first exhausting every known method of 
physical and laboratory study. He was a hard taskmaster to 
himself both as a practitioner and as a consultant and left no 
step unconsidered which would assist his fellow worker and 
colleague or be of assistance to the sick and ailing patient. 
Theodore Janeway was trained under the exacting conditions 
of a large consulting practice in a large city. He nevertheless 
never became commercial and showed a remarkable aptitude 
for applying scientific methods to the study of clinical medi- 
cine and for stimulating others to pursue a career in the re- 
search laboratories connected with his hospital wards. His 
ability in this field has meant much to New York in general 
and to the College of Physicians and Surgeons in particular. 

It was the special opportunity of the college to call Theo- 
dore Janeway to the career of a teacher in a broad field and to 
raise him at one step from an instructorship of associate grade 
to the highest position in clinical medicine within the gift of 
Columbia University, the Bard Professorship of the Practice 
of Medicine. He succeeded in his task from the outset and 
became widely known in New York and the whole country as 
a teacher w^ho could analyze the process of reasoning which 
led to his diagnosis, who possessed the art of graphic descrip- 
tion to an unusual degree and who instilled in his students and 
in the instructors of his department a rigid thoroughness in 
routine and an exact precision in thought and expression. 

As an executive Theodore Janeway w-as familiar with every 
detail of his department. He was always accessible to his col- 
leagues for counsel and eager to consider advice from an assis- 
tant as from an equal. He was earnestly devoted to his con- 
ception of the right and ready to fight or to make any personal 
sacrifices for his ideals. He left his mark on New York medi- 
cine by taking charge of a department bare of every facility 
for modern teaching and research and after a short four years 
he left it equipped with a library, which had been his own, 
with a hospital service, with research laboratories and with the 
nucleus of a staff" devoted to teaching and to research. Colum- 
bia University and New York were that much poorer when he 
left to assume the work in Baltimore at Johns Hopkins. 

There are in New York many younger men in the profession 
who have impressed on me, since the untimely death of Theo- 
dore Janeway, their sense of personal loss and their gratitude 
to him for an oarlv insight into the high ideals of medicine. 



June, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



145 



for an appreciation of the necessity for absolute medical hon- 
esty and the need for a constant revision of opinion as new 
facts are discovered and for having labored with a man devoted 
to a thorough and systematic habit of work. 

It was my personal privilege to start Theodore Janeway as a 
student on his medical career and to be among the first to 
teach him, to whom I later went to learn. It is my present 
privilege to add my testimony to his worth as a clinician, to 
his ability as a teacher, to his loyalty to his friends and to the 
permanent impress for good which he made on medical educa- 
tion in New York City. His work and character are remem- 
bered there as an exponent of all that is good and all that is 
best in a profession which is still controlled by ideals ; a pro- 
fession which is still advanced by the power of the human 
brain and hand to do the most perfect work in a world so 
largely controlled and ruled by the machinery of construction 
and of destruction. 

Dr. David Edsall. — In periods of great change in thought 
and policy and in the nature of individual responsibilities 
clear vision, high purpose, and a determined idealism tempered 
by wide judgment, are qualities of such importance as to over- 
balance others. Doubtless in all times of great activity and 
change in work of whatever sort these qualities have seemed 
to be needed as never before. We should not do justice to 
our forbears in medicine if we exalted too far above theirs the 
tasks that have fallen upon those to whom we have looked for 
leadership,' but we nevertheless can but believe that in the 
past two or three decades, the complexities and responsibilities 
of medicine have been largely added to and there have been 
in progress and in prospect such fundamental changes, not 
only in knowledge but in policy, that qualities and training 
fitting for wise guidance have been especially demanded and 
more desirable than any others. And in recent times the 
greater weight of these new responsibilities has fallen upon 
clinician.s, for the non-clinical branches had passed through 
their most acute travail earlier and had become somewhat 
adjusted to the changes when the clinician met the need of 
a new alignment in viewpoint and in manner of life and 
thought. To the clinician the complexity has been increased 
by the need of retaining much that his colleagues could cast 
off and nevertheless of readjusting his methods in much the 
same manner as they. He has had to add a multiplicity 
of precise methods to the earlier less exact ones that demanded 
chiefly training in observation and interpretation, but he 
has been obliged to retain undiminished his regard for the 
latter. He has had need to undergo the still more difficult 
mental adjustment to experimental instead of observational 
methods of thought and especially of research, as the yield 
from the older methods became less fruitful; and yet he has 
had to retain a cautious respect for even purely empirical 
observations. In academic medicine he has had to make deci- 
sions and adjustments similar to those of his colleagues in the 
distribution of his energies and in manner of life, but he has 
had to cherish and to train equally the power of human under- 
standing and the patient study of character and the attention 



to petty affairs that are so spendthrift of time and energy-, but 
without which lie would overlook his main duty, the safe- 
guarding of individual himian life and health. 

These changes liave been of gradual growi;h but Theodore 
Janeway passed through the period of most rapid transforma- 
tion, the period in which alterations have been at times so 
sudden and radical as to arouse wide differences of opinion, 
and in which clear judgment and determination have been 
needed to avoid undue haste and enthusiasm as against com- 
placent inertia. 

Long training with his distinguished father and a very lovely 
veneration of him would of themselves have sufficed to prevent 
him from being led by enthusiasm for the newer types of study 
to belittle the value of those methods that made Edward Jane- 
way so eminent. But by temperament as well, Theodore Jane- 
way was conspicuously attached to and he was rarely gifted in 
the painstaking clinical and pathological observation of disease, 
and through years of accumulated study of literature of disease 
in its progress and of its pathological results, he acquired that 
skill and clarity in the observation and discussion of matters of 
diagnosis and treatment that left no one his superior as a clini- 
cian or as a contributor to directly practical clinical medicine 
and gave him his exceptional strength as a teacher of practice. 

Clinical medicine, especially in its research activities, was 
coming constantly closer to the laboratory and it was inevit- 
able that this rapprochement should become increasingly in- 
timate. But general sympathy with this essential movement 
could be secured early and its progress hastened far more 
through keen appreciation of what was good in the older meth- 
ods as well as the new than through a partisan championship of 
the new alone. It was a great and permanent service that Theo- 
dore Janeway rendered to medicine in furnishing so fine and 
timely and so outstanding a demonstration that a man may be 
a devoted master in the older methods and at the same time an 
eager student and contributor in the new, and likewise a stimu- 
lus and guide equally to those whose pathway leads them chiefly 
into the one or the other and especially to those who would 
co-ordinate the two. Nothing has been more needed. No 
one has done it so well. To have had great opportunity and 
power to exert influence upon the things that mould the char- 
acter of one's i^rofession and to have used them so as to have 
left debtor both radical and conservative is a singularly rare 
and valuable service. His success in this was in part due to 
the training and judgment that I have indicated, in part to a 
very broad fund of knowledge ever at the service of others, but 
no less than to these it was due to that type of ardent sjonpathy 
and idealism that leaves a bit of fire in those it touches. To 
many who came close to him even occasionally there must stand 
out as more helpful even than his contributions to knowledge 
the picture of a nobiUty of purpose, an abimdant sympathy 
and comprehension, fired by that trace of desire for the unat- 
tainable whicli, when restrained by sanity of judgment, lifts 
up a leader to reach the attainable and without which even 
genius secures few disciples; and to those engaged in the 
study of problems in any branch of medicine there will always 
remain a keen and trratcful memory of the inspiring thought- 



146 



JOHNS HOPKINS HOSPITAL BULLETIN 



[Xo. 328 



fulness with which he constantly kept their work in mind 
and put at their service as few remember to do anything 
helpful that came up in his own busy work. 

And this catholic sympathy and interest extended beyond 
his labors for the individual sick and for those who deal with 
them alone. He comprehended clearly the interdependence of 
health and of many community problems and of the ways in 
which the physician may attach himself to social movements 
and still remain within the fields for which his training fits 
him. He was one of a very few in medicine to whom those 
who struggle with these problems turned confidently for wise 
advice and generous aid and yet he saw clearly the limits 
as well as the extent of the physician's province in these mat- 
ters. Peculiarly devoted as he was to the human relations of 
the practice of medicine, whatever the recompense, it was in 
very considerable part a great sacrifice to relinquish for purely 
academic work and increased burdens of administration the 
grateful intimate personal side of the life of the physician 
who is chosen by the patient, a loss that he did not cease to 
feel. But when the choice had to be made it was at once 
made with sole thought of the way in which he could best 
meet the needs of medicine. This decision was typical of 
an attitude of mind that was and will remain a powerful 
part of his influence upon medicine. 

There is a comforting sweetness to those who held him per- 
sonally very dear in the generous evidence of the breadth and 
variety of his influence that comes from those in all these 
varied forms of work that the clinician meets in normal times. 
Never greatly endowed with vigor he had constantly in 
civil conditions " ventured life and love and health " ever 
with the unselfish thought of service. It is but natural that 
all these should have been ventured again, ventured then, 
alas, finally, in single-hearted loyalty to his country after 
having given in this work further distinguished exhibition of 
skill and Judgment in organizing and placing men and in the 
determination of methods and policies. 

To have been a wise and trusted pilot in his- high calling, 
to have helped signally to weld together opposing and disor- 
ganizing forces, to have guided clearly juniors and contem- 
poraries not only in deeds but in motives, and to have left 
a light burning in all the forms of his high endeavor, to have 
done all these is to have done more potent things than are 
often done. 

A thought that has become commonplace through repetition 
may still seem new and moving when we recall it as wo 
first met it. When I think of the problem of immortality, 
I always go back to my boyhood to the time when I heard 
a cold, repressed, unreligious man, after listening apparently 
uninterested to a discussion of such matters, say suddenly and 
with a sternness that still arrests my attention that what- 
ever one feels about a future life, immortality of some dcTee 
and kind is inevitable for all of us. that we can not prevent 
the indefinite perpetuation of our influence for good or evil 
even though the source of the influence may soon become 
untraceable and unnamable. 



" Not till the hours of light return, 
All we have built do we discern." 

If we can visualize the increasing growth of the wave from 
an impulse as it passes on from group to group we may find 
recompense for the unaccountable brevity of a high career in 
the enduring influence of a true and strong force that will 
still act when other more prolonged energies have become 
relatively spent and inert. 

Major General William C. Gorgas, Surgeon General, TJ. S. 
Army. — My acquaintance with Dr. Janeway began originally 
when he was a little child. In the early days of my medical 
career I was house physician in Bellevue Hospital and in 
the division over which Dr. Janeway, St., Dr. Flint and Dr. 
Lusk presided, three names to conjure with in the province of 
medicine. 

The elder Dr. Janeway at that time was much interested in 
the pathological work of his division, and it was my duty there 
to be associated with him and to assist in his researches. 
Through my visits to Dr. Janeway's house, I first met the 
younger Dr. Janeway, as I have said, as a little child. In 
after life I met him occasionally at the meetings of medical 
societies and other gatherings of our profession. At that time 
I knew him only as an eminent professional man. 

On the entry of our nation into the present war, it became 
necessary for my office to find men prominent in civil life, 
above the average mark in their profession, to assist in the 
selection of those who were to serve as my staff in building up 
the large machinery which is necessary in the conservation of 
the health of the armed forces. 

I appealed to Dr. Janeway to take over the direction of an 
important division in the office, and he, as was so characteristic 
of him, promptly gave up his work in Baltimore almost 
entirely and devoted himself heart and soul to the furtherance 
of the interests of his country here in Washington. He was 
with me up to the time of his death and organized in a most 
efficient manner the division of which he was the head. 

As the head of the Medical Corps, his death was a keen 
loss to me, aside from the regret which I feel at the death of 
a friend whom I trusted and admired. 

In all the machinery of a busy oflicc, such as ours in 
Washington, there is not much time for personal intercourse, 
but I did see Dr. Janeway many times in consultation over 
matters concerning the routine of his division. 

Less than a month before his death, I had occasion to in- 
spect with him some of the southern camps. Our contact at 
that time was close and intimately personal, for we lived and 
travelled together for a considerable length of time. Know- 
ing Dr. Janeway in this way personally, for the first time, I 
was much drawn to him and attracted by the fineness of his 
character; by his constant cheery manner; his optimistic 
outlook in the face of any difficulty. The work during this 
trip was hard and exacting, the days often mounting up to 
eight and ten hours of constant work ; but in the face of it 
all, he was ever patient, ever alert and always bright and 
checrfnl. T feel (hat it was a privilege to know in this inti- 



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JOHNS HOPKINS HOSPITAL BULLETIN 



147 



mate wa_y the personal side, as well as to realize, as I have 
for a long time, the fine qualities of his professional mind. 

One of the former speakers has made a remark which ap- 
pealed to me strongly. He has brought np the question as 
to whether it is altogether regrettable for a man to die in his 
prime, at the height of his power and vigor and force. In 
reading military history, I have often thought that no sol- 
dier's death was more fortunate than that of Stonewall Jack- 
son, a man who had risen in two years to a position in his 
profession probably never excelled by any of his predecessors 
of the English speaking race. His military career had been 
eminently successful and was markedly so in the battle in 
which he gave his life for his cause. It had been a day of 
unexampled success; he had extricated his chief from an ap- 
parently impossible position; at the moment when he was 
stricken down he was following a routed and defeated army ; 
so far as he could see, his course was successful. What greater 
or more welcome death could a soldier have than to be called 
at such a time? 

Viewed from this aspect, I cannot think that Dr. Jane- 
way's death is altogether regrettable. He was at the prime of 
life and at the period of exaltation from personal success. He 
had made his name honored and admired. Of course, we who 
are left behind see it differently, for apparently Dr. Janeway 
had within him more years of useful work for his fellow man, 
and I, as Surgeon General, cannot but feel the loss which 
his death means in the work to which I am pledged. 

But from the standpoint of the individual, if we had to 
choose our period of death, would most of us take the time 
when our faculties have begun to deteriorate, when we are old 
and past the prime, or would we prefer to finish our career 
when we are strong and sure and in the full vigor of all accom- 
plishment? 

And so, today I stand in a double capacity : as the Surgeon 
General of the Army, I feel keenly the loss of an almost 
essential part of my organization. As a man and a friend, 
I feel that sense of personal loss which is inevitable at the 
departure of those we love. 

Dr. William H. Welch.— There is little indeed to add to 
the tributes which have already been paid to our beloved 
friend and colleague, Dr. Theodore Janeway. He has been 
spoken of as the " younger Janeway " and reference has very 
appropriately been made of his father, who was a great influ- 
ence in his life. His inheritance, manifested by those remark- 
able traits of mind and character, was the very best on the 
paternal and maternal side. His native endowments were 
high. To those were added an admirable education adapted 
to his peculiar qualities, and with a view to his profession. 
He was trained at the Yale Scientific School, and there he 
followed that course which was in no small part organized and 
developed by the first president of this university. President 
Oilman, at the time he was connected with the scientific 
school at Yale. That was the first course inaugurated which 
took into consideration the need of specialized training for 
those who contemplated the study of medicine. 



With this inheritance and this training, Dr. Janeway en- 
tered upon the study of medicine in New York. He graduated 
at Columbia University, but his education only then began. 
It continued through his life. 

As I have said the greatest influence was that of his father. 
Like General Gorgas I also had the privilege of coming under 
the inspiration of the elder Janeway, who was surely one of the 
most remarkable men in our profession in our generation, 
indeed in the medical history of our country. A man whom 
future generations I think can hardly estimate as we who 
knew him estimated him, because he was not a prolific writer. 
His influence was personal and sprang from his knowledge, 
character and scientific spirit, his absorbing interest and zeal — 
it was from those qualities he inspired those who came close 
to him. His services were of the highest character. Every 
institution with which he was connected received an impres- 
sion from him. 

Dr. Lambert has indicated the great debt which Columbia 
LTniversity and the Presbyterian Hospital owe to Dr. Jane- 
way. While in New York, he also had to do with the work- 
ing out of the gift of ilrs. Eussell Sage, for promoting scien- 
tific medicine. While there he was also elected one of the 
scientific directors of the Eockefeller Institute, to succeed Dr. 
Christian Herter, and his voice on our board was always 
most valuable. On behalf of my colleagues on the board of 
directors of the Rockefeller Institute for Medical Research, 
I desire to express our sense of personal loss in his death. 

He was a good citizen. He was interested in the modern 
problems of society and although his devotion to his profession 
was almost single-minded, he did find time to give to some 
very interesting social questions and there he rendered great 
service. He was a good doctor and a good citizen. 

AVe were most fortunate in securing Dr. Janeway as the first 
professor of medicine under the foundation which enabled 
this university to institute what we believe to be a great reform 
in clinical teaching. Through the generosity of the Rocke- 
feller Foundation, we were enabled to establish three of our 
chairs on what we call the " University Basis." The imder- 
lying principle is that in the time to come, those who devote 
themselves to the responsible work of teaching, to the care 
of patients in the hospital and to research in the laboratory, 
shall make that their occupation and life work. The principle 
appealed to Dr. Janeway and although his experience led him 
to feel there might be some modifications of certain of the 
requirements, he was himself and always remained heartily in 
sympathy with the fundamental conception. I think it was 
always a great satisfaction to him that he was called upon 
the first to serve in the most important chair in a medical 
scbool— that of Medicine — and to develop the clinic along 
these newer lines. He rendered unforgettable service in tliis 
capacity for which the university must always retain a feel- 
ing of gratitude. 

If I may be permitted, I would like to emphasize the great 
service which he, under Col. Bushnell, rendered to our army 
and therefore to our country. In the opportunities which I 
have had with General Gortras in visiting our camps, it has 



148 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 328 



been the greatest satisfaction to find that there was always 
a first class medical man at the head of the medical service 
in the camp hospitals. These physicians and their staffs were 
selected for this service by Dr. Janeway. He often had to 
persuade some doctor, usually a successful and active practi- 
tioner of the right age for this service, that his duty was to 
give up his practice and to enter the army for this work. It 



is a great satisfaction to all of his friends to feel, as has been 
so well expressed by the Surgeon General, that he was able to 
render this great service to his country. He felt intensely 
about the war and was glad that he had an opportunity to 
serve. He would not have done differently if he had foreseen 
all that was to come. I think we may say he died as truly 
in the service of his country as if he had fallen in battle. 



DR. JOHN HALL: SHAKESPEARE'S SON-IN-LAW ^ 

Bv Eli ]\Ioschcowitz, A. B., M. D. 



The physician whose story I propose to tell you to-night 
was not born great ; he did not achieve greatness ; he had great- 
ness thrust upon him. He blazed no trail in medicine; nor, 
like some of our calling who were not even great as doctors, 
did he distinguish himself in the sister sciences, the arts, the 
pursuit of the Muses, or the love of his fellow-men. He was 
just an ordinary general practitioner. He little dreamed, on 
the day he took Shakespeare's daughter as his bride, that he 
was rescuing himself from a deserved oblivion. 

What then is the purpose of celebrating a person of such 
slender pretensions to fame? Even the pride we naturally 
feel that the son-in-law of Shakespeare was a physician would 
not suffice to commemorate John Hall. It so happens, how- 
ever, that he wrote a book of case reports gleaned from his own 
practice, which, medically speaking, is of no value, but yet is 
of interest to us because it affords a fair record of the state of 
medical practice in his day. But above all it has an intenser 
and wider interest, because, avid as we are for every fact, no 
matter how trivial, that brings us into contact with Shake- 
speare, this book draws us into a close acquaintance with Shake- 
speare's family and social circle. And so to-night instead of 
ranging the Mounts of Olympus, we shall nestle, for a fleeting 
moment, by the fireside of William Shakespeare. 

The direct stimulus to this study was the opportunity to 
peruse the rare volume written by John Hall and published 
for the first time in 1657." It is duodecimo, and bears the 
following inscription on the fly leaf ( Fig. 1 ) : " Select obser- 
vations on English Bodies; or, cures both empericall and his- 
toricall, performed upon very eminent persons in desperate 
diseases. First, written in Latine by Mr. John Hall, 
Physician, living in Stratford upon Avon in Warwick-shire, 
where he was very famous, as also in the counties adjacent, as 
appears by these observations drawn out of severall hundreds 
of his, as choysist. Now put into English for common benefit 
by James Cooke, Practitioner in Physick. and Chirurserv. 
Ijondon, printed for John Slierley, at Golden Pelican, in 
Little Brittain, 1657." 

John Ilnll, who married Shakespeare's eldest daughter. 
Susanna, in her 25th year at Stratford on June 5, IGO;, was 



' Read before the Historical Section of tlie New Yorlc Academy 
of Medicine, October, 1917. 

= I am indebted to the Walpole Galleries of New York City for 
this privilege, for which I thank them. 



born in 1575, and although he was a master of arts, he never 
attained a medical degree. How he obtained his medical 
knowledge is not known. In his youth, as usual at that time 
with people of means, he traveled on the continent. Just 
when he arrived at Stratford is not known ; the first notice of 
any record of him is his marriage to Susanna, so that it is 
quite probable that he settled in Stratford only after his 
marriage. The only other records of Hall during Shake- 
speare's lifetime, is one in 1611, when his name is found in the 
list of supporters to a highway bill, and one in 1612, when he 
leased a small piece of woodland on the outskirts of the town. 
The Halls lived in a house in the thoroughfare leading to the 
church in a part of Stratford known as the Old Town. The 
house is still standing (Fig. 2) and bears the name of Hall's 
Croft. At all events, here he acquired an extensive practice 
and bore a considerable local reputation as a skilled physician, 
as shown by the fact, recorded in his book, that he was often 
called to treat the Earl or Countess of Northampton, 40 miles 
away. Dr. Hall apparently was a person of importance in the 
town of Stratford, for in 1617 and in 1623 he was elected a 
burgess, but for unknown reasons he was excused from under- 
taking office. In 1632, he was again elected and accepted the 
office. He quarreled with his associates concerning the matter 
of fines for non-attendance and other matters, and in October. 
1633, he was expelled after the following resolution had been 
passed : " At this Hall, Mr. John Hall is displaced from being 
a Capitall Burgesse by the Voices and Consent of Nineteene of 
the Com]iany, as appeared by the letter r at there names, for 
the breech of orders wilfully, and sundry other misdemeanors 
contrary to the duty of Burgesse and the oath which he hath 
taken in this place, and for his continual disturbance at our 
Halles, as will appear by the particulars." That he was a man 
of strong passions is also shown by tlie Linacre professor who 
translated his book from Latin into English for Dr. Cooke, 
and who says of him in the preface that " Such as hated him 
made use of him," The professor probably refers especially 
to Hall's deep religious convictions. He was an avowed 
Protestant with puritanical leanings, which became more pro- 
nounced as he grew older. Indeed, it is upon Hall, who was 
executor and, with his wife, residuary legatee of Shakespeare's 
will, that most of the blame is laid for the loss of Shakespeare's 
mannsi'ri|its of his jilays. 



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JOHNS HOPKINS HOSPITAL BULLETIN 



149 



He died November 25, 1635, and was buried in the parish 
churchyard. His tombstone records the following inscription : 
Here lyeth ye Body of John Halle gent. He marr. Susanna 
daugh. (co-heire) of Will. Shakespare gent. Hee deceaseil 
Nove. 25, A : 1635. Aged 60. 

Hallius hie situs est, medica celeberrimus arte: 

Expectans regni gaudia laeta Dei; 
Dignus erat meritis qui Nestora vinceret annis, 

In terris omnes sed rapit aequa dies. 
Ne tumulo quid desit, adest fidissima conjux, 

Et vitae comitem nunc quoq; mortis habet 

Hall's book, which reports 200 cases, was written in Latin. 
The manner in which the book was published is interesting and 
reveals a human touch so Boswellian, that nothing that we 
know of Shakespeare himself approaches it in intimacy. In 
1642, during the Civil Wars, Surgeon Cooke, on duty with a 
regiment guarding a bridge over the Avon, was acquainted by 
a friend that Mrs. Hall had some books and manuscripts 
which her husband had left behind him.' He visited her at 
New Place and, " after a view of them Mrs. Hall told me she 
had some books left by one that professed physic with her hus- 
band for some money. I told her, if I liked them I would give 
her the money again ; she brought them forth, amongst which 
there was this [referring to the book] with another of the 
authoi's I)oth intended for the press. I being acquainted with 
Mr. Hall's hand, told her that one or two of them were her 
husbands and showed them her; she denied, I affirmed, till I 
perceived she began to be offended ; at last I returned her the 
money." This shows, first, that Susanna apparently inherited 
some of the business acumen of her father. It also reveals that 
she cared more for money than for books. It also shows that 
either her education was not sufficient to enable her to detect 
her own husband's handwriting (her own signature (Fig. 3 ) 
reveals anything but a practiced hand), or, that she did not 
want it to appear that she was willing to part with anything 
belonging to her husband, to whom, as we shall see, she was 
closely attached. At all events, Cooke took it to London to 
have it translated by the Linacre professor mentioned above. 

The book evidently had a reasonable popularity, probably 
as a household manual, for it went into two editions, in 1679 
and 1683. Certainly the appeal to the general public must 
have been very strong, for all the 200 case reports are cures. 

From the contents of the book, I gather that Dr. Hall was 
a general practitioner, with little or no leanings to surgery. 



'Tlie will of John Hall. "The Last Will and Testament non- 
cupative of John Hall of Stratford-upon-Avon in the county of 
Warwick, gentleman, made and declared the five and twentieth 
of November 1635. Imprimis, I give unto my wife my house in 
London. Item, I give unto my daughter Nash, my house in Acton. 
Item, I give unto my daughter Nash, my meadowe. Item, I give 
my goodes and money unto my wife and my daughter Nash to be 
equally divided betwixt them. Item, — concerning my study of 
books, 1 leave them, sayd he, to you, my son Nash, to dispose of 
them as you see good. As to my manuscripts, I would have given 
them to Mr. Boles, if he had been here, but inasmuch as he is not 
heere present, you may, son Nash, burne them, or doe with them 
what you please. Witness, thereunto, Thomas Nash, Simon Trapp." 



His patients cover a wide social range, including lords, earls, 
Ijaronets, countesses, squires, Catholicks, goodwives, gentlemen, 
barbers, maids, household servants and children. The earliest 
case report of which any date is furnished is that of Lord 
Compton, who was attended previously to his lordship's de- 
parture to Scotland with the king in 1617. 

Medically speaking, as I have said, the book is of no value. 
Dr. Hall was probably no worse and probably a little better 
than the average country practitioner of his time. The book 
does not bear evidence of having been written for the eye of 
the medical fraternity, so that he had little occasion to reveal 
the depths of his learning. There is no clinical observation, 
diagnoses are paraphrased into colloquial parlance, the pre- 
cision of diagnosis seems intended to impress infallibility ; — all 
in all, the case reports are merely the barest outlines and serve 
as delicate frameworks upon which to hang the elaborate and 
inevitable cure. The materia medica employed by Hall is 
extensive, consisting largely of the Galenical plants, with 
occasionally such medijeval remedies as the dried windpipe 
of a cock and the dung of various animals. It mirrors largely 
the therapeutical combination of superstition and empiricism 
of his time. 

The diseases cured by Hall are of the most diverse sort. We 
may well envy Dr. Hall, who cures by the simplest means 
diseases in which we, the possessors of a heritage of centuries 
of the most brilliant discoveries, feel nearly helpless. Thus 
he reports many cures of dropsy, the falling sickness, melan- 
choly, sterility, enuresis, cancer, etc. Be that as it may, the 
diseases mentioned in Hall's book cover a wide range. Gyneco- 
logical diseases are common ; postpartum sepsis, sterility, " the 
whites," dysmenorrhea and menorrhagias. Scurvy seems to 
have been especially common ; also round worms. In addition 
we find various fevers, including " Enterick " and " Tertian." 
constipation and other intestinal disorders, especially " the 
colick," respiratory disorders, gonorrhea, etc. 

Commentators have speculated freely upon where Shake- 
speare derived his amazing knowledge of medicine. I venture 
to suggest that Shakespeare was indeljted largely to Dr. Hall. 
Certainly he knew his son-in-law for at least nine years, and 
perhaps longer, before he died, and probably they were no more 
averse to discussing professional matters with one another, 
than men in the same professions are to-day. Another leading 
circumstance, is the fact, as Dr. M. Kahn of this city pointed 
out to me, that most of Shakespeare's knowledge of things 
medical is displayed in his tragedies, most of which were 
written in the later years of his life. 

And now we come to the more passionate interest that this 
book bears. Had Dr. Hall written nothing but the case reports 
of obscure persons, the book to-day would have been only a 
curiosity, the mere prey of the collector of Shakesperiana. 
Fate has so ordained, however, that Dr. Hall hapi>ened to 
include among his case reports the illnesses of persons known 
to the immortal William himself, so that with another stroke 
of luck, Hall raises himself from the position of an obscure 
relative of Shakespeare to the dignity of an historian. 



150 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 328 



Some were relatives, many were his close friends. Thus 
we find two references to his daughter Susanna, Hall's wife; 
Hall's only daughter, Elizabeth, Shakespeare's granddaughter, 
upon whose death in 1670 Shakespeare's direct lineage ceased; 
Hall's own sickness is recounted. Also that of Michael Dray- 
ton, the poet, with whom Shakespeare and Ben Jonsou, accord- 
ing to Vicar Ward's testimony, " had a merrie meeting, but 
Shakespeare seems drank too hard, for he died of a fever there 
contracted." This is the only scrap of information we possess 
of the manner of Shakespeare's death. Indeed, it is not a 
great stretch of fancy to think that Dr. Hall may have attended 
Shakespeare during his last illness, and had Hall been as will- 
ing to risk his failures as his cures for publication, we might 
have found Shakespeare's last illness recorded here. We also 
find the case of Mr. Q.ueeny who was, undoubtedly, that 
Richard Quiney who died in 1602, and after whose wife Shake- 
speare's eldest daughter Susanna was named. He was a 
mercer, and bears the distinction of being the author of the 
only extant letter to Shakespeare, in which he appealed for a 
loan of money in 1598. His son, Thomas Quiney, married 
Shakespeare's second daughter Judith. Mrs. Sadler (p. 13) 
must have been Judith Sadler after whom Shakespeare's 
second daughter was named. Hamnet Sadler's name was 
given to Shakespeare's only son. Hamnet Sadler was an inti- 
mate friend and one of the beneficiaries under Shakespeare's 
will. Anne Ward (p. 212) may have been related to the Vicar 
of Stratford to whom we are indebted for the only account of 
Shakespeare's death. A Captain Bassett, who is mentioned 
twice, may have been the original of the character of that name 
found in King Henry VI, Part 1. 

The following case reports, which have been selected either 
for their human or their medical interest, serve to indicate the 
character of Dr. Hall's book : 

" Obs. 19. Mrs. Hall of Stratford my wife, being miserably tor- 
mented witii the colicli, was cured as foUoweth; 5 Diaphaen. 
Diacatholic. anaji; Lact. q. s. f. Clyst. This Injected gave two 
stools, yet the pain continued, being but little mitigated, there- 
fore I appointed to inject a pint of sack made hot, this presently 
brought forth a great deale of wind, and freed her from all pain, to 
her stomach was applyed a plaster de Labd. Cret. cum Canan. et 
Spec. Aromat. rosat. et 01. Macis. With one of these glysters I 
delivered the Earle of Northampton from a grievous colick. 

Obs. 36. Elizabeth Hall, my onely daughter was vexed with 
totura oris or the convulsion of the mouth, and was happily cured 
as followeth. First I exhibited these pills; IJ Pil. Coch. et Aureas, 
ana 5 i; f. pil. 10. She took five the first day which gave her seven 
stooles. I fomented the part with Theriac. Androniac. and Aq. 
Vitae. To her neck was used this, IJ. Lingu. Martiat. Magn. ^i; 
01. Laverin. petrolei, Castor, et Terebinth, ana 5 iss de lateri- 
bus 5i; misce. by this she had great advantage, her courses being 
obstructed, thus I purged her. 1^. Pil. foetid. 31 Castor 5i; 
de Succin. rhab. egaric. ana 3 i; f. Mass. she took five pills in 
the morning," etc. 

The account of l-IIizabetli is extreiucly long, so I shall abl)re- 
viate the remainder. On January 5, 1624, she had an oph- 
thalmia. In April she went to London ; on the 22d she 
returned home. She took cold and " fell into the said dis- 
temper on the contrary side of her face." On May 24 she was 
attacked by " enterick " fever, which he also duly cured. 



I have summarized the report of his own illness, because in 
the original, it is too long. Pious man that he was, he prefaces 
his account with a prayer. 

Obs. 60. (2) "Thou O Lord who has the power of life and 
death, and drawest from the fates of death. I confesse without any 
art or counsell of Man, but only from thy goodnesse and clemency; 
Thou has saved me from the bitter and deadly symptoms of a 
deadly fever, beyond the expectation of all about me, restoring me 
as it were from the very jaws of death to former health, for which 
I praise thy name, most merciful God, and Father of Our Lord 
Jesus Christ, praying Thee to give me a most thankful! heart for 
this great favor, for which I have cause to admire Thee." 

On August 27, 1632, in the 57th year of his age, he had an 
attack of severe hemorrhoids. He was constipated 14 days; 
nevertheless, he says, that he " was constrained to visit many 
of his patients." A fever followed. He first purged with 
rhubarb. A delirium set in, which was cured l)y " opening a 
live pidgeon and applyed to his feet to draw down the vapors." 
At this part of his illness, his wife became alarmed, so two 
physicians were called into consultation who again purged him 
fully, and prescribed a formidable host of drugs. In the mean- 
time, " § vii of blood was drawn from the liver veine and 
leeches were applyed to the haemorrhoids." During the con- 
valescence he took Chalybeate Wine as a tonic, and was troubled 
with a scrotal itch w-hich was cured with a " decoction of 
sarsparilla with antiskorbutick herbs." 

" Obs. 22. Mr. Drayton an excellent Poet, labouring of a 
Tertian was cured by the following IJ. The Emetick infusion; 
Syrup of violets a spoonful, mix them; this given, wrought very 
well both upwards and downwards." 

Obs. 38. The report of Mr. Queeney's illness is distin- 
guished by the fact that a troublesome cough was treated with 
a gimshot prescription containing 28 ingredients. This appar- 
ently proved inefl^ectual, for soon after Dr. Hall ordered his 
head to be shaved and in addition prescribed four additional 
prescriptions. Then follows the only report of a fatality 
throughout the book. " Being not wholly freed from it, he fell 
into it again next year, all remedies proving successless, lie 
dyed. He was a good wit, expert in tongues and very learned." 

I shall cite only a few of the case reports that are of unusual 
medical interest. Gynecologists may be interested in the three 
following cases : 

" Obs. 52. Mrs. Sheldon, wife to the son, being corpulent, well 
coloured, was wont to miscarry often, the second month after con- 
ception, yet suffered no other accident with it, required my counsel, 
I advised her to purge, and strengthen the womb, for which she 
took sage in her drinks and meats, also a little of the following in 
a raw egg. IJ Gran, tinctor. Marjorit. tormentili ana .ii; 
Mastic. 5 iss misc. f. pil. there was given as much as would lie on 
a groat. For the retaining the infant, this is the best plaster. 
5 Labd. puris. 5 iss Gallar. Mirtel. Ros. Rub. Sang. Dracon. 
balanst. ana s iss pil. Naval. 3 ii Tereb. 3 vi Malax, omnia simul, f. 
Empl. part of which spread on leather, and applyed to the loynes, 
OS sacrum, and the bottome of the Belly. This she used all her 
time, and after brought fortli a lusty hearty son, and after that 
more." 

" Obs. 26. Mrs. Broughton of Causon, aged 28. Three days 
after miscarriage in the fifth moneth fell into a fever accompanied 
with abundance of after-fluxes, vomiting, loathing, thirst, swoon- 



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151 



ing, and in danger of death was speedely helpt as followeth. 
y burnt Hartshorn finely powdered 5 i; boyl it in three quarts 
of Spring water till a quart be wasted, then remove it from the 
fire, after adde syrup of Lemons 5ii; rose water 5 iv, sugar a 
suflicient quantity. This she drank constantly instead of drink, 
which gave great ease. The following decoction was given 
morning and evening, which did dense, cure, cast out, and ex- 
tinguish thirst. 5 French barley vfi iv violets P ii, liquiris 3 iss, 
jujebs 5i; Sebestens 5ii; carduus benedictus ni^iss; make a 
decoction in sufficient quantity of water to lb xii to the straining, 
adde sugar of violets and make a drink. By these medicines 
alone she was cured beyond all expectation." 

" Obs. 47. (second series). My Lady Rainsford, beautiful and 
of a gallant structure of body, near 27, was three days after her 
being laid of her child, miserably tormented with pain in her 
belly, from which I delivered with the following. IJ the white of 
Hens Dung 5i; being put in beer and sugar, she took it. To the 
belly the following was applyed hot. 5 New milk and Honey, 
each It) i horehound ttl i; wheat flour 5 iii, seffron; 3 i; boyl them 
to a pultis. By these she was delivered." 

The following reports are of pediatric interest: 

" Obs. 35. A child of Mr. Walkers of Ilmington, minister, aged 
six moneths afilicted with falling-sickness, by consent was thus 
freed. First, I caused round pieces of piony root to be hanged 
about the neck, when the fit afflicted I commanded to be applyed 
with a spunge to the nostrils the juyce of Rue mixt with Wliite 
Wine Vinegar, by the use of which it was presently recovered, 
and falling into the fit again, it was removed in the same manner. 
To the region of the heart was applyed the following. IJ Theriac. 
Ver. 3 ii Rad. palon. pul. 3 ss misc. The haire was powdered with 
powder of the roots of pioney and thus the child was delivered 
from all its fits." 

Here is a case that Dr. Cullen might introduce into the next 
edition of his monumental work on Diseases of the Umbilicus : 

" Obs. 98. Dixwell Brunt of Pillerton, aged 3, had a tumor of the 
navil, out of which broake five long wormes out of a little hole, 
like a fistula; the nurse pull out tour dead, but the fifth was 
somewhat alive; the forepart moveing, the hinder part stirred, 
as witnessed the nurse. Father, Mother and Maide; the tumor 
being hard, I appoynted a plaster of hony to be applyed, but no 
wormes appeared; the next day was applyed a Cataplasme of 
green Wormwood, beat with the gall of an oxe, and boyled. 
There was given a suppository. After these the navil was cured 
and he lived. 

" Obs. 60. Talbot the first born of the Countess of Salisbury, 
aged about one yeare, being miserably afflicted with a fever and 
wormes, so that death was onely expected, was thus cured. There 
was first injected a glyster of milk and sugar, this gave two 
stooles, and brought away four wormes. By the mouth was given 
Hartshorn burnt, prepared in the farme of a julep. To the pulse 
was applyed, Ungu. Papuleon 5ii; mixt with spider's webs and a 
little powder of nut shells. It was put to one pulse of one wrist 
one day and to the other the next. To the stomach was applyed 
Mithridate, to the navel the Emplaster against wormes. And thus 
he became well in three days, for which the Countess returned 
me many thanks, and gave me a great reward." 

Hall was not bound too rigidly by the rules of professional 
secrecy as the report of the following case reveals. Here is 
how Hall cures a gonorrhea : 

" Obs. 80. William Clavel troubled witli a virulent gonnorrhea 
and extreme heat of urine, having been under anothers hands for 
a moneth without profit was cured with the following remedyes 
In fifteen days space, being in the moneth of November. 1^ Gum 



Guaiac pul 3 i ; it was given in beer, it gave five stooles. After- 
wards he took a pint of the following decoction morning and 
night. 5 Sarsp. Jii; Hermodactyles 5 iss; Guaiacum, Liquiris, 
each Ji; Seny 3i; Seeds of Anis Carraway and Cariander, 
each Jss; boyl them in eight pints of water till half be wasted. 
After the strained liquor was taken, there was given the following 
electuary. 5 Gum Tragacanth Jss; dissolve it in sufficient 
quantity of plantain water, strain it, adde gum Guaiacium pow- 
dered 3ii; Terebinth burnt 3 i, mix them. Dos. 3 iss; By the use 
of the decoction of Sarsa. he was very well purged, and delivered 
altogether from pain in the loynes and heat of the urine in four 
dayes, and by the use of the electuary he was altogether cured of 
his gonnorrhea." 

It now only remains, as in the last chapter of a novel, to 
relate the fate of some of the characters that have passed before 
our gaze. There is a melancholy interest in this telling, because 
we find that all of Shakespeare's descendants died before the 
end of the seventeenth century, so that the most prodigious and 
universal mind the world has ever known had but a brief 
blossoming. You may remember that Shakespeare and Anne 
Hathaway had three children ; a son, Hamnet, and two 
daughters, the younger Judith, the elder Susanna. Hamnet 
died in his 12th year during the poet's lifetime in 1596. 
Judith married some two months before the- father's death, 
Thomas Quiney, son of the Kichard Quiney mentioned in 
Dr. Hall's book. The bride was 32 years old ; her husband was 
her junior by four years. Thomas Quiney was a vintner, and 
l)ecame a chamberlain and a burgess of Stratford. He became 
involved in much litigation, had financial reverses and moved 
to London, where, apparently, he died in poverty. The Quineys 
had three sons, Shakespeare who died in infancy, and Richard 
and Thomas, who both died soon after reaching manhood. 
iVs neither of the latter had issue, the line of the poet in this 
direction became extinct in 1662 when their mother, aged 77, 
died. 

Of Susanna, Dr. Hall's wife, we know little except that in 
1613, during Shakespeare's lifetime, she brought a suit for 
defamation of character against a John Lane, Jr., who had 
circulated a libelous rumor of immoral conduct. The slan- 
derer, however, failed to appear, and a .sentence of excom- 
munication was passed against him. She died July 11, 1649, 
and her tombstone is marked with the following verse : 
" Witty above her sexe, but that's not all. 

Wise to Salvation was good Mistress Hall, 

Something of Shakespere was in that, but this 

Wholy of him with whom she's now in blisse. 

Then, passenger, ha'st ne're a teare. 
To weepe with her that wept with all? 

That wept, yet set herselfe to chere 
Them up with comforts cordial 1. 

Her Love shall live, her mercy spread, 

When thou hast ne're a teare to shed." 

The Halls' only child, Elizabeth, was nine year old when her 
grandfather died. She married in Stratford in 1626, Thomas 
Nash, a Stratford resident of considerable property. Born in 
1593, he was a student at Lincoln's Inn. His father and uncle 
were intimate friends of Shakespeare. Mrs. Nash became a 
widow in 1647, and two years later married John Barnard, a 



152 



JOHNS HOPKINS HOSPITAL BULLETIN 



[No. 338 



gentleman of wealth. Having no issue by either husband, the 
last descendant of William Shakespeare died in 1670 ; and so, 
like an organ peal in the dusk, the lines of her immortal grand- 
father's first sonnet serve as a fitting close : 

"From fairest creatures we desire increase, 

That thereby beauty's rose might never die, 

But as the riper should by time decrease 

His tender heir might bear his memory; 

But thou, contracted to thine own bright eyes, 

Feeds't thy light's flame with self-substantial fuel. 

Making a famine where abundance lies, 

Thyself thy foe, to thy sweet self too cruel. 



Thou that are now the world's fresh ornament 
And only herald to the gaudy spring. 
Within thine own bud buriest thy content 
And, tender churl, makest waste in niggarding; 
Pity the world, or else this glutton be. 
To eat the world's due, by the grave and thee." 



REFERENCES 
Select Observations on English Bodies. John Hall. Ed. Cooke, 
1657. 
Outlines of the Life of Shakespeare. Halliwell-Phillipps, 1898. 
A Life of William Shakespeare. Sidney Lee. New York, 1909. 



PROCEEDINGS OF SOCIETIES 



THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY 

JANUARY 7, 191S 
1. Demonstration of a Duodenectomized Dog. (Abstract.) 
Dk. Eknest G. Gkay. 
In the course of some experiments liaving to do with the 
effects of the diversion of the pancreatic juice into the stomach 
upon the level of gastric acidity it became desirable to extir- 
pate the duodenum. A review of the literature, however, dis- 
closed no record of a successful duodenectomy. This portion of 
the intestinal tract was first removed by Minkowski, but as 
his experiments and those of subsequent workers only covered 
a period of a few weeks no evidence exists concerning the ulti- 
mate effects of such an extirpation. The principal reason, prob- 
ably, why it has been impossible to keep animals living for 
any considerable length of time following this operation, is 
that the endeavors to re-establish a channel of communication 
between the pancreas and the intestinal tract have all been 
without result. 

A new problem then presented itself, the question as to 
whether the surgical difficulties encountered in the course of 
the excision of the duodenum might be successfully met. It 
is the results of some work bearing on this subject to which I 
wish to refer tonight. 

Experiments dealing with this problem were started about a 
year ago. Of a series of dogs used for tliis purpose one animal 
survived the various operative procedures, some died of pneu- 
monia, others of distemper, etc. The extirpation was carried 
(Hit ill three stages. At the first operation the gall-bladder 
was anastomosed to the proximal jejunum and the common bile 
duct doubly ligated and divided. Some time subsequent to 
til is the major pancreatic duct was dissected from the duo- 
denal wall and transplanted into the jejunum a short distance 
from the site of the cholecystenterostomy opening. Then in 
a third stage the entire duodenum was extirpated and end-to- 
end anastomosis made between the antrum of the stomach and 
the proximal jejunum. In order to preserve the vascular sup- 
ply of the pancreas a very narrow strip of the muscular coat of 
the duodenum (on the side of the bowel facing the pancreas) 
was left attached to the pancrcatico-duodenal vc^;sels. The 
margins of this layer of muscle cells were then irnshcil and 
stitched together In eciiiln.l l)leedilig. 



The duodenum was removed from the dog which you see 
before you eight and one-half months ago. Each of the three 
abdominal wounds healed per primam. Since the resection the 
animal has gained about 6 ounces in weight (a small fox 
terrier), his appetite being rather above that of a normal dog. 
Eepeated tests have never revealed the existence of any gly- 
cosuria. The stools have been normal in appearance. 
Throughout the past eight months the dog has continued in 
excellent health and has always been as active as he appears 
tonight. 

The results of the experimental work just outlined demon- 
strate conclusively, first, that a dog may remain in good health 
following a total duodenectomy, and second, that the pancreas 
may be successfully connected with the intestinal tract after 
the removal of the entire duodenum. 

2. The Origin of tlie Corpus Luteum. Dn. G. W. Corner, San Fran- 

cisco, Calif. 

3. On the Absorption of Drugs and Poisons from the Vagina. 

(Abstract.) Du. Daviu L Macut. 

While a large number of drugs are introduced into the 
vagina in the form of douches, tampons, suppositories, "uterine 
wafers," etc., and while a search in clinical literature reveals 
undoubted cases of poisoning occurring through this channel, 
no experimental work except that of a clinical character 
is on record on the subject. In connection with tlie study of 
the question of absoi-ption of drugs through unusual channels, 
the author undertook a systematic study concerning absorp- 
tion of drugs and poisons from the vagina. A large number 
of drugs were investigated in this connection : Alkaloids, esters, 
antiseptics, and dissociable salts. As a criterion or proof of 
absorption, both physiological and chemical evidence was 
obtained. It was found that drugs of all kinds are absorbed 
surprisingly rapidly from the vagina. Thus, for instance, a 
few milligrams of apomorphin or morphin introduced into 
the vagina of a dog produced vomiting within five minutes. 
Among the alkaloids studied were : MorpJiin, apomorphin, pilo- 
carpine, atropine, cocaine and aconitiu. Undoulited proof 
of absorption of various salts was given by experiments with 
potassium iodide, potassium ferrocyanide and potassium cyan- 
ide. Nitrofflveeriiip is raiiidlv al)sori)Oil from the vagina; so 



i 



June, 1918] 



JOHNS HOPKINS HOSPITAL BULLETIN 



153 



also are the nitrites of sodium and jjotassiuni. Of the antisep- 
tics studied the chief ones were phenol, cresol and corrosive 
sublimate. All these were found to be very rapidly absorbed as 
evidenced by physiological and toxicological symptoms and 
also by chemical tests. The full paper on the subject appears 
in the Journal of Pharmacology and Experimental Therapeu- 
tics, Volume X, page 509, January, 1918. In the paper, in 
addition to the experimental data, an exhausti